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| Mendeliome v0.9083 | PRICKLE2 | Zornitza Stark Mode of inheritance for gene: PRICKLE2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9078 | COPB2 | Zornitza Stark Mode of inheritance for gene: COPB2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9075 | UBE2U |
Ee Ming Wong gene: UBE2U was added gene: UBE2U was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBE2U was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UBE2U were set to PMID: 33776059 Phenotypes for gene: UBE2U were set to Retinoschisis; cataracts; learning disabilities; developmental delay Penetrance for gene: UBE2U were set to Complete Review for gene: UBE2U was set to RED gene: UBE2U was marked as current diagnostic Added comment: - one missense UBE2U variant identified in one family with four other affected individuals (includes proband) - in silico analyses predicts the UBE2U variant to be damaging - no functional - another STUM missense variant identified in the same family predicted to be benign - additional clinical assessment indicated that the family shared some systemic dysmorphisms and learning disabilities similar to RIDDLE syndrome Sources: Literature |
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| Mendeliome v0.9072 | GRIK2 | Zornitza Stark Mode of inheritance for gene: GRIK2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9068 | CACNA1I |
Kristin Rigbye gene: CACNA1I was added gene: CACNA1I was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CACNA1I was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA1I were set to 33704440 Phenotypes for gene: CACNA1I were set to Neurodevelopmental disorder Mode of pathogenicity for gene: CACNA1I was set to Other Review for gene: CACNA1I was set to GREEN Added comment: 4 different missense variants identified and shown to result in a gain of function. 2 individuals with de novo variants (a 3rd also suspected de novo but their father was unavailable for testing) - these patients all had severe neurodevelopmental disorders, involving severe global developmental delay, absence of speech, gross motor delay, muscular hypotonia, early-onset seizures, cortical visual impairment, and feeding difficulties. Variable clinical features include various brain malformations, startle response or seizures, postnatal growth retardation, gastroesophageal reflux, and gastrostomy. 1 family had three affected individuals - variable cognitive impairment in all, involving borderline intellectual functioning or mild or moderate intellectual disability as main clinical feature, with late-onset seizures in the mother and speech retardation in one of the children. This variant had a milder functional effect than the variants in sporadic cases. Sources: Literature |
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| Mendeliome v0.9068 | ZNF668 |
Paul De Fazio changed review comment from: 5 individuals from 3 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts. Sources: Literature; to: 2 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts. Sources: Literature |
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| Mendeliome v0.9067 | ZNF668 |
Paul De Fazio changed review comment from: 5 individuals from 3 consanguineous families reported with different truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts. Sources: Literature; to: 5 individuals from 3 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts. Sources: Literature |
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| Mendeliome v0.9067 | CFAP206 |
Ain Roesley gene: CFAP206 was added gene: CFAP206 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP206 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CFAP206 were set to Multiple morphological abnormalities of the fagella Penetrance for gene: CFAP206 were set to unknown Review for gene: CFAP206 was set to AMBER Added comment: 1x hom with a fs variant Sperm from knockout mouse model mainly had a fagellum of normal length but most of them showed abnormal forms including bent and coiled fagella. There was also a significant increase of sperm cells with absent or short fagella compared to the WT mice. Sources: Literature |
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| Mendeliome v0.9067 | ZNF668 |
Paul De Fazio gene: ZNF668 was added gene: ZNF668 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF668 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF668 were set to 34313816; 26633546 Phenotypes for gene: ZNF668 were set to DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism Review for gene: ZNF668 was set to GREEN gene: ZNF668 was marked as current diagnostic Added comment: 5 individuals from 3 consanguineous families reported with different truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts. Sources: Literature |
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| Mendeliome v0.9067 | GLIS1 |
Seb Lunke gene: GLIS1 was added gene: GLIS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GLIS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GLIS1 were set to 34385434 Phenotypes for gene: GLIS1 were set to Increased ocular pressure Review for gene: GLIS1 was set to RED Added comment: Functional studies in KO mice show increased intra-ocular pressure (IOT) caused by defects in the ocular drainage system. IOT is frequently associated with Glaucoma, however mice were not investigated for glaucoma, and no patients described. Sources: Literature |
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| Mendeliome v0.9065 | SLC32A1 |
Zornitza Stark gene: SLC32A1 was added gene: SLC32A1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC32A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLC32A1 were set to 34038384 Phenotypes for gene: SLC32A1 were set to Genetic epilepsy with febrile seizures plus Review for gene: SLC32A1 was set to GREEN Added comment: 8 unrelated families reported, including segregation evidence in two large pedigrees. Variants are predicted to alter γ-aminobutyric acid (GABA) transport into synaptic vesicles, leading to altered neuronal inhibition. Sources: Literature |
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| Mendeliome v0.9061 | G6PD | Zornitza Stark Mode of inheritance for gene: G6PD was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9058 | EPB42 | Zornitza Stark Mode of inheritance for gene: EPB42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9055 | EPB41 | Zornitza Stark Mode of inheritance for gene: EPB41 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9052 | DHFR | Zornitza Stark Mode of inheritance for gene: DHFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9049 | CYB5R3 | Zornitza Stark Mode of inheritance for gene: CYB5R3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9046 | CD59 | Zornitza Stark Mode of inheritance for gene: CD59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9043 | NEDD4L | Zornitza Stark Mode of inheritance for gene: NEDD4L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9038 | AMN | Zornitza Stark Mode of inheritance for gene: AMN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9035 | AK1 | Zornitza Stark Mode of inheritance for gene: AK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9032 | ALAS2 | Zornitza Stark Mode of inheritance for gene: ALAS2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9029 | ABCG5 | Zornitza Stark Mode of inheritance for gene: ABCG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9026 | TOM1 |
Zornitza Stark gene: TOM1 was added gene: TOM1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TOM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TOM1 were set to 31263572 Phenotypes for gene: TOM1 were set to Immunodeficiency 85 and autoimmunity, MIM# 619510 Review for gene: TOM1 was set to RED Added comment: Parent and child reported with onset of atopic eczema and recurrent respiratory infections in the first decade of life; autoimmune enteropathy with vomiting, diarrhoea, and poor overall growth. More variable features included autoimmune oligoarthritis, interstitial pneumonitis, and EBV viremia. Laboratory studies showed hypogammaglobulinaemia and abnormal T-cell function, consistent with a combined immunodeficiency. Missense variant in TOM1, with limited functional data. Sources: Expert list |
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| Mendeliome v0.9025 | GINS2 |
Arina Puzriakova gene: GINS2 was added gene: GINS2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GINS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GINS2 were set to 34353863 Phenotypes for gene: GINS2 were set to Meier-Gorlin syndrome with craniosynostosis Review for gene: GINS2 was set to RED Added comment: Sa et al., 2021 (PMID: 34353863) identified a patient presenting with prenatal and postnatal growth restriction, a craniofacial gestalt of MGORS and coronal craniosynostosis. A homozygous missense variant (c.341G>T, p.Arg114Leu) in GINS2 was identified that was heterozygous in both unaffected parents. Some supportive functional data included. GINS2 is not currently not associated with any phenotype in OMIM or G2P and no additional cases have been identified to date. Sources: Literature |
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| Mendeliome v0.9021 | CHRM1 |
Bryony Thompson gene: CHRM1 was added gene: CHRM1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CHRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHRM1 were set to 34212451; 31981491; 12483218 Phenotypes for gene: CHRM1 were set to Neurodevelopmental delay; intellectual disability; autism Review for gene: CHRM1 was set to AMBER Added comment: PMID: 34212451 - 2 unrelated cases with de novo missense variants (p.Pro380Leu and p.Phe425Ser), one case with early-onset refractory epilepsy, severe disability, and progressive cerebral and cerebellar atrophy, and the second case with mild dysmorphism, global developmental delay, and moderate intellectual disability. In vitro biochemical analyses of p.Pro380Leu demonstrated a reduction in protein levels, impaired cellular trafficking, and defective activation of intracellular signaling pathways. PMID: 31981491 - an autism spectrum disorder (no other information on phenotype, except ascertained to have severe neurodevelopmental delay) case with a de novo missense variant p.(Arg210Leu) PMID: 12483218 - null mouse model assessing memory demonstrated selective cognitive dysfunction. Sources: Literature |
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| Mendeliome v0.9019 | FGF20 |
Zornitza Stark gene: FGF20 was added gene: FGF20 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FGF20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FGF20 were set to 22698282 Phenotypes for gene: FGF20 were set to Renal hypodysplasia/aplasia 2, MIM#615721 Review for gene: FGF20 was set to AMBER Added comment: Multiple affected fetuses in a consanguineous family; functional data. Sources: Expert Review |
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| Mendeliome v0.9016 | ITGA8 | Zornitza Stark Mode of inheritance for gene: ITGA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9013 | NPR2 | Zornitza Stark Mode of inheritance for gene: NPR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9010 | RPS6KA3 | Zornitza Stark Mode of inheritance for gene: RPS6KA3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9009 | SHOX2 |
Zornitza Stark gene: SHOX2 was added gene: SHOX2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SHOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SHOX2 were set to 30443179 Phenotypes for gene: SHOX2 were set to Sinus Node Dysfunction; Atrial Fibrillation Review for gene: SHOX2 was set to RED Added comment: Single family reported with LoF in this gene and AF. Sources: Expert Review |
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| Mendeliome v0.9005 | KCTD7 | Zornitza Stark Mode of inheritance for gene: KCTD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9001 | ROR2 | Zornitza Stark Mode of inheritance for gene: ROR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8998 | PROP1 | Zornitza Stark Mode of inheritance for gene: PROP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8995 | WRN | Zornitza Stark Mode of inheritance for gene: WRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8992 | POU1F1 | Zornitza Stark Mode of inheritance for gene: POU1F1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8990 | OPDM2 |
Bryony Thompson STR: OPDM2 was added STR: OPDM2 was added to Mendeliome. Sources: Literature Mode of inheritance for STR: OPDM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: OPDM2 were set to 32413282; 33374016 Phenotypes for STR: OPDM2 were set to Oculopharyngodistal myopathy 2 MIM#618940 Review for STR: OPDM2 was set to GREEN STR: OPDM2 was marked as clinically relevant Added comment: NM_005716.4:c.-211GGC[X] >15 Chinese families/probands with a heterozygous trinucleotide repeat expansion (CGG(n)) in 5'UTR exon 1 of the GIPC1 gene. The expansion was found by a combination of linkage analysis, whole-exome sequencing, long-range sequencing, and PCR analysis, and segregated with the disorder in the family. Repeat lengths in the patients ranged from 70 to 138. Normal repeat lengths ranged from 12 to 32. Sources: Literature |
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| Mendeliome v0.8987 | FAME2 |
Bryony Thompson STR: FAME2 was added STR: FAME2 was added to Mendeliome. Sources: Literature Mode of inheritance for STR: FAME2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: FAME2 were set to 11701600; 24114805; 31664034 Phenotypes for STR: FAME2 were set to Epilepsy, familial adult myoclonic, 2 MIM#607876 Review for STR: FAME2 was set to GREEN STR: FAME2 was marked as clinically relevant Added comment: NM_020151.3(STARD7):c.291-1572ATTTT[X]ATTTC[X] 158 affected individuals from 22 unrelated families with familial adult myoclonic epilepsy with a heterozygous 5-bp repeat expansion (ATTTC)n in intron 1. Affected individuals had variable expansion of an endogenous (ATTTT)n repeat in addition to the insertion of an abnormal (ATTTC)n repeat, similar molecular finding in other forms of FAME. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and no effect on STARD7 gene expression, suggesting ATTTC expansions may cause FAME irrespective of the genomic locus involved. Sources: Literature |
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| Mendeliome v0.8981 | PI4KA | Zornitza Stark edited their review of gene: PI4KA: Added comment: Neurodevelopmental syndrome with hypomyelinating leukodystrophy: 10 unrelated patients harbouring biallelic variants in PI4KA reported with a spectrum of severe global neurodevelopmental delay, hypomyelination, and developmental brain abnormalities, and pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Western blotting and immunofluorescence showed decreased PI4KA levels in the patients' fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells.; Changed rating: GREEN; Changed publications: 25855803, 34415322; Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8980 | NIID |
Bryony Thompson STR: NIID was added STR: NIID was added to Mendeliome. Sources: Literature Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102; 34333668 Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Oculopharyngodistal myopathy 3 MIM#619473; Tremor, hereditary essential, 6 MIM#618866 Review for STR: NIID was set to GREEN STR: NIID was marked as clinically relevant Added comment: NM_001364012.2:c.-164GGC[X] Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2. Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease. Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier. Intermediate range: 41-60 identified in Parkinson's disease Pathogenic repeat range: >=60-520 Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals. Sources: Literature |
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| Mendeliome v0.8977 | SUCO |
Bryony Thompson gene: SUCO was added gene: SUCO was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SUCO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SUCO were set to 29620724; 20440000 Phenotypes for gene: SUCO were set to Osteogenesis imperfecta Review for gene: SUCO was set to AMBER Added comment: A single case with diffuse osteopenia, multiple fractures with limb deformities, and short long bones, with biallelic variants (a missense and a splice site variant). Also, a null mouse model with acute onset skeletal defects that include impaired bone formation and spontaneous fractures. Sources: Literature |
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| Mendeliome v0.8974 | IGFALS | Zornitza Stark Mode of inheritance for gene: IGFALS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8972 | FAME1 |
Bryony Thompson STR: FAME1 was added STR: FAME1 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: FAME1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for STR: FAME1 were set to 30194086; 29507423 Phenotypes for STR: FAME1 were set to Epilepsy, familial adult myoclonic, 1 MIM#601068 Review for STR: FAME1 was set to GREEN STR: FAME1 was marked as clinically relevant Added comment: NC_000008.10:g.119379055_119379157TGAAA[X]TAAAA[X] A heterozygous or homozygous 5-bp expanded TTTCA(n) insertion associated with an upstream 5-bp TTTTA(n) repeat expansion in a noncoding region within intron 4 of the SAMD12 gene, was identified in over 50 Chinese and Japanese families. 4 homozygous cases from 3 families had a more severe phenotype. The TTTTA repeat was present in controls, while the TTTCA was absent and only present in cases (100-3680 repeats reported). RNA toxicity is expected to be the mechanism of disease. Sources: Expert list |
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| Mendeliome v0.8969 | MYO1H |
Zornitza Stark gene: MYO1H was added gene: MYO1H was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYO1H was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYO1H were set to 28779001 Phenotypes for gene: MYO1H were set to Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction, MIM#619482 Review for gene: MYO1H was set to RED Added comment: Single family reported with three affected children, homozygous LoF variant. Sources: Literature |
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| Mendeliome v0.8966 | BLM | Zornitza Stark Mode of inheritance for gene: BLM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8963 | PRKDC | Zornitza Stark Mode of inheritance for gene: PRKDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8960 | TBX1 | Zornitza Stark Mode of inheritance for gene: TBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8959 | TBX1 | Zornitza Stark Tag SV/CNV tag was added to gene: TBX1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8957 | RTEL1 | Zornitza Stark Mode of inheritance for gene: RTEL1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8954 | RMRP | Zornitza Stark Mode of inheritance for gene: RMRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8951 | RFX5 | Zornitza Stark Mode of inheritance for gene: RFX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8947 | TYK2 | Zornitza Stark Mode of inheritance for gene: TYK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8944 | RAG1 | Zornitza Stark Mode of inheritance for gene: RAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8941 | RAG2 | Zornitza Stark Mode of inheritance for gene: RAG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8937 | RAC2 | Zornitza Stark Mode of pathogenicity for gene: RAC2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8936 | RAC2 | Zornitza Stark Mode of inheritance for gene: RAC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8933 | GLI2 | Zornitza Stark Mode of inheritance for gene: GLI2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8930 | GHSR | Zornitza Stark Mode of inheritance for gene: GHSR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8925 | GHRHR | Zornitza Stark Mode of inheritance for gene: GHRHR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8922 | GHR | Zornitza Stark Mode of inheritance for gene: GHR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8920 | SCA12 |
Bryony Thompson STR: SCA12 was added STR: SCA12 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA12 were set to 27864267; 33811808 Phenotypes for STR: SCA12 were set to Spinocerebellar ataxia 12 MIM#604326 Review for STR: SCA12 was set to GREEN STR: SCA12 was marked as clinically relevant Added comment: NM_181675.3:c.27CAG[X] Uncertain if CAG repeat encodes polyglutamine or instead effects expression of specific splice variants of the encoded phosphatase Normal: ≤32 repeats Uncertain: ~40-50 repeats have been reported, 43 repeats is the lowest reported in an established affected individual in a family with SCA12 Established pathogenic (used as diagnostic cut-off): ≥51 repeats Sources: Expert list |
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| Mendeliome v0.8915 | WDR11 | Zornitza Stark Mode of inheritance for gene: WDR11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8911 | GH1 | Zornitza Stark Mode of inheritance for gene: GH1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8908 | EPHX1 | Zornitza Stark Mode of inheritance for gene: EPHX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8898 | TRPS1 | Zornitza Stark Mode of inheritance for gene: TRPS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8895 | FGD1 | Zornitza Stark Mode of inheritance for gene: FGD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8892 | BRD4 | Zornitza Stark Mode of inheritance for gene: BRD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8889 | ZNF699 |
Zornitza Stark gene: ZNF699 was added gene: ZNF699 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF699 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF699 were set to 33875846 Phenotypes for gene: ZNF699 were set to DEGCAGS syndrome, MIM# 619488 Review for gene: ZNF699 was set to GREEN Added comment: DEGCAGS syndrome is a neurodevelopmental disorder characterized by global developmental delay, coarse and dysmorphic facial features, and poor growth and feeding apparent from infancy. Affected individuals have variable systemic manifestations often with significant structural defects of the cardiovascular, genitourinary, gastrointestinal, and/or skeletal systems. Additional features may include sensorineural hearing loss, hypotonia, anaemia or pancytopaenia, and immunodeficiency with recurrent infections. 12 unrelated families reported, 5 different homozygous frameshift variants. Sources: Literature |
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| Mendeliome v0.8880 | PAPPA2 |
Zornitza Stark gene: PAPPA2 was added gene: PAPPA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PAPPA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAPPA2 were set to 26902202; 34272725; 32739295 Phenotypes for gene: PAPPA2 were set to Short stature, Dauber-Argente type, MIM#619489 Review for gene: PAPPA2 was set to GREEN Added comment: Short stature of the Dauber-Argente type (SSDA) is characterized by progressive postnatal growth failure, moderate microcephaly, thin long bones, and mildly decreased bone density. Patients have elevated circulating levels of total IGF1 due to impaired proteolysis of IGFBP3 and IGFBP5, resulting in reduced free IGF1. 7 individuals from 3 unrelated families reported, mouse model. Sources: Literature |
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| Mendeliome v0.8877 | ATR | Zornitza Stark Mode of inheritance for gene: ATR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8875 | SHOX | Zornitza Stark Mode of inheritance for gene: SHOX was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8874 | SHOX | Zornitza Stark Tag SV/CNV tag was added to gene: SHOX. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8872 | ORC4 | Zornitza Stark Mode of inheritance for gene: ORC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8869 | ORC1 | Zornitza Stark Mode of inheritance for gene: ORC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8866 | ORC6 | Zornitza Stark Mode of inheritance for gene: ORC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8863 | IGF1 | Zornitza Stark Mode of inheritance for gene: IGF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8862 | IGF2 | Zornitza Stark Mode of inheritance for gene: IGF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8859 | OBSL1 | Zornitza Stark Mode of inheritance for gene: OBSL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8856 | PIK3R1 | Zornitza Stark Mode of inheritance for gene: PIK3R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8853 | PLAG1 |
Zornitza Stark edited their review of gene: PLAG1: Added comment: Additional families reported, upgrade to Green. Silver-Russell syndrome-4 (SRS4) is characterised by intrauterine growth retardation followed by feeding difficulties and postnatal growth restriction. Dysmorphic facial features include triangular face and prominent forehead, and relative macrocephaly at birth may be observed. So far 4 families have been reported with some functional studies of the role of the gene in the growth pathway. Abi Habib et al. (2018) reported 1 family (child, sister and mother) patient with Silver-Russell syndrome (with normal methylation on chromosomes 7, 11, and 14, and exclusion of maternal UPD and chromosomal rearrangements). Using WES they identified a heterozygous 1-bp deletion in the PLAG1 gene. The variant segregated with disease, and was not present in polymorphism databases or ExAC. They also reported another patient with a different heterozygous 1-bp deletion in the PLAG1 gene. This was not found in her unaffected twin brother, older brother, or parents. Experiments in Hep3b cells demonstrated that PLAG1 positively regulates expression of the IGF2 promoter P3, independently and via the HMGA2-PLAG1-IGF2 pathway. Disruption of any gene in the pathway results in a decrease in IGF2 expression and produces an SRS phenotype similar to that of patients carrying 11p15.5 epigenetic defects (SRS1; 180860), except for body asymmetry, which is not expected to occur since the molecular defects are present in all cells of the body, unlike the mosaic epigenetic changes at the 11p15.5 locus. Inoue et al. (2020) reported 1 family with 2 affected people with Silver-Russell syndrome with a nonsense variant in the PLAG1 gene, which segregated with disease. Vado et al. (2020) reported 1 family with multiple affected people with Silver-Russell syndrome with a frameshift variant in the PLAG1 gene, which segregated with disease.; Changed rating: GREEN; Changed publications: 28796236, 29913240, 33291420, 32546215 |
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| Mendeliome v0.8851 | WIPF1 | Zornitza Stark Phenotypes for gene: WIPF1 were changed from to Wiskott-Aldrich syndrome 2 MIM# 614493; Reduced T cells; defective lymphocyte responses to anti-CD3; high IgE; Thrombocytopenia with or without small platelets; recurrent bacterial and viral Infections; eczema; bloody diarrhoea; gastrointestinal bleeding; WAS protein absent | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8849 | WIPF1 | Zornitza Stark Mode of inheritance for gene: WIPF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8845 | TCN2 | Zornitza Stark Mode of inheritance for gene: TCN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8842 | TAP2 | Zornitza Stark Mode of inheritance for gene: TAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8839 | TAP1 | Zornitza Stark Mode of inheritance for gene: TAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8837 | PGRMC1 | Bryony Thompson Tag SV/CNV tag was added to gene: PGRMC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8836 | WIPF1 | Danielle Ariti reviewed gene: WIPF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22231303, 27742395, 11869681, 14757742; Phenotypes: Wiskott-Aldrich syndrome 2 MIM# 614493, Reduced T cells, defective lymphocyte responses to anti-CD3, high IgE, Thrombocytopenia with or without small platelets, recurrent bacterial and viral Infections, eczema, bloody diarrhoea, gastrointestinal bleeding, WAS protein absent; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8835 | ALS2 |
Teresa Zhao gene: ALS2 was added gene: ALS2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALS2 were set to PMID: 30128655; 33409823 Phenotypes for gene: ALS2 were set to Infantile onset ascending spastic paralysis (MIM#607225); Juvenile amyotrophic lateral sclerosis 2 (MIM#205100); Juvenile primary lateral sclerosis (MIM#606353) Review for gene: ALS2 was set to GREEN Added comment: >50 variants reported in multiple individuals with Infantile onset ascending spastic paralysis, mostly originated from the Middle East and Mediterranean countries. Sources: Literature |
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| Mendeliome v0.8835 | RNF220 | Zornitza Stark Tag founder tag was added to gene: RNF220. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8834 | RNF220 |
Zornitza Stark gene: RNF220 was added gene: RNF220 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNF220 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNF220 were set to 33964137; 10881263 Phenotypes for gene: RNF220 were set to Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum Review for gene: RNF220 was set to GREEN Added comment: Sferra et al (2021 - PMID: 33964137) provide extensive evidence that biallelic RNF220 mutations cause a disorder characterized by hypomyelinating leukodystrophy, ataxia (9/9 - onset 1-5y), borderline intellectual functioning (3/9) / intellectual disability (5/9 - in most cases mild), sensorineural deafness (9/9) with complete hearing loss in the first decade of life, hepatopathy (9/9) with associated periportal fibrosis, and dilated cardiomyopathy (9/9) which was fatal. Other neurologic manifestations apart from ataxia incl. hyperreflexia (8/8), spastic paraplegia (9/9), dysarthria (9/9), peripheral neuropathy (4/9), seizures in one case (1/9). Upon brain MRI there was thin corpus callosum (9/9) or cerebellar atrophy in some (2/9). The authors identified homozygosity for 2 recurrent missense RNF220 variants in affected members belonging to these 5 broad consanguineous pedigrees (7 families), namely NM_018150.4:c.1094G>A / p.Arg365Gly in 4 Roma families in the context of a shared haplotype (/founder effect) as well as c.1088G>A / p.Arg363Gly in a large pedigree from southern Italy initially reported by Leuzzi et al (2000 - PMID: 10881263). Extensive segregation analyses were carried out including several affected and unaffected members. RNF220 encodes ring finger protein 220, which functions as an E3 ubiquitin ligase. Previous studies have shown among others a role in modulation of Sonic hedgehog/GLI signaling and cerebellar development Evidence for the role of RNF220 included relevant expression, localization within the cell, interaction partners (lamin B1, 20S proteasome), similarities with other laminopathies in terms of phenotype, etc : *RNF220 has a relevant expression pattern in CNS (based on qRT-PCR analyses in human brain, cerebellum, cerebral cortex / mRNA levels in human fetal CNS with higher expression in cerebellum, spinal cord and cortex / previous GTEx data / protein levels in mouse CNS) *The protein displays nuclear localization based on iPSC cells differentiated to motor neurons (also supported by data from the Human Protein Atlas). Transfection of COS-1 cells demonstrated localization primarily to the nucleus (as also previously demonstrated in HEK293T cells) in vesicle like structures with ASF2/SF2 colocalization suggesting enrichment in nuclear speckles. There was also partial co-distribution with the 20S proteasome. R363Q and R365Q additionally coalesced in the cytoplasm forming protein aggregates/inclusions. *Immunofluorescence studies in patient fibroblasts also confirmed abnormal increase of the protein in the cytoplasm and increased fluorescence with the 20S proteasome. *Proteomic identification of RNF220-interacting proteins in transfected HEK293T cells demonstrated enrichment for all members of the lamin protein family (incl . lamin B1, AC, B2). *RNAi-mediated downregulation of RNF222 in Drosophila suggested altered subcellular localization and accumulation of the fly orthologue for human lamin B1. *Immunoprecipitation of lamin B1 from the nuclear matrix of cerebellar cells suggested significant interaction of endogenous lamin B1 with RNF220, while transfection studies in HEK293T cells for wt/mt suggested reduced binding to endogenous lamin B1 for RNF220 mt compared to wt (more prominent for R365Q). RNF220 mutants also reduced ubiquitination of nuclear lamin B1 compared to wt. *Patient fibroblasts immunostained with different nuclear envelope markers displayed abnormal nuclear shapes with multiple invaginations and lobulations, findings also observed in laminopathies. Sources: Literature |
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| Mendeliome v0.8831 | NBAS | Zornitza Stark Mode of inheritance for gene: NBAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8829 | ARF3 |
Zornitza Stark gene: ARF3 was added gene: ARF3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARF3 were set to 34346499 Phenotypes for gene: ARF3 were set to Global developmental delay; Intellectual disability; Seizures; Morphological abnormality of the central nervous system Review for gene: ARF3 was set to AMBER Added comment: Sakamoto et al (2021 - PMID: 34346499) provide some evidence that monoallelic ARF3 pathogenic variants may be associated with a NDD with brain abnormality. Using trio exome sequencing, the authors identified 2 individuals with NDD harboring de novo ARF3 variants, namely: NM_001659.2:c.200A>T / p.Asp67Val and c.296G>T / p.Arg99Leu. Individual 1 (with Asp67Val / age : 4y10m), appeared to be more severelely affected with prenatal onset progressive microcephaly, severe global DD, epilepsy. Upon MRI there was cerebellar and brainstem atrophy. Individual 2 (Arg99Leu / 14y) had severe DD and ID (IQ of 23), epilepsy and upon MRI cerebellar hypoplasia. This subject did not exhibit microcephaly. Common facial features incl. broad nose, full cheeks, small philtrum, strabismus, thin upper lips and abnormal jaw. There was no evidence of systemic involvement in both. ARF3 encodes ADP-ribosylation factor 3. Adenosine diphosphate ribosylation factors (ARFs) are key proteins for regulation of cargo sorting at the Golgi network, with ARF3 mainly working at the trans-Golgi network. ARFs belong to the small GTP-binding protein (G protein) superfamily. ARF3 switches between an active GTP-bound form and an inactive GDP-bound form, regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) respectively. Members of the ARF superfamily regulate various aspects of membrane traffic, among others in neurons. There are 5 homologs of ARF families, divided in 3 classes. ARF3 and ARF1 belong to class I. Monoallelic ARF1 mutations are associated with Periventricular nodular heterotopia 8 (MIM 618185). In vivo, in vitro and in silico studies for the 2 variants suggest that both impair the Golgi transport system although each variant most likely exerts a different effect (gain-of-function for Arg99Leu vs loss-of-function/dominant-negative for Asp67Val). This was also reflected in somewhat different phenotype of the subjects with the respective variants. Common features included severe DD, epilepsy and brain abnormalities although Asp67Val was associated with diffuse brain atrophy as well as congenital microcephaly and Arg99Leu with cerebellar hypoplasia. Evidence to support the effect of each variant include: Arg99Leu: Had identical Golgi localization to that of wt Had increased binding activity with GGA1, a protein recruited by the GTP-bound active form of ARF3 to the TGN membrane (supporting GoF) In silico structural analysis suggested it may fail to stabilize the conformation of Asp26, resulting in impaired GTP hydrolysis (GoF). In transgenic fruit flies, evaluation of the ARF3 variant toxicity using the rough eye phenotype this variant was associated with increased severity of the r-e phenotype similar to a previously studied GoF variant (Gln71Leu) Asp67Val: Did not show a Golgi-like pattern of localization (similar to Thr31Asn a previously studied dominant-negative variant) Displayed decreased protein stability In silico structural analysis suggested that Asp67Val may lead to compromised binding of GTP or GDP (suggestive of LoF) In transgenic Drosophila eye-specific expression of Asp67Val (similar to Thr31Asn, a known dominant-negative variant) was lethal possibly due to high toxicity in very small amounts in tissues outside the eye. There is no associated phenotype in OMIM, G2P or SysID. Sources: Literature |
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| Mendeliome v0.8826 | CEP57 | Zornitza Stark Mode of inheritance for gene: CEP57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8824 | PLXNA2 |
Zornitza Stark gene: PLXNA2 was added gene: PLXNA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLXNA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLXNA2 were set to 34327814 Phenotypes for gene: PLXNA2 were set to Intellectual disability; Abnormality of the face; Failure to thrive; Abnormal heart morphology Review for gene: PLXNA2 was set to AMBER Added comment: Altuame et al (2021 - PMID: 34327814) describe 3 individuals from 2 consanguineous Arab families with biallelic PLXNA2 variants. The index patient from the 1st family presented with CHD (hypoplastic right ventricle, ASD), DD and moderate ID (IQ of 40), failure to thrive as well as some dysmorphic features (obtuse mandibular angle, mild overbite, synophrys with downslanting p-f, strabismus, etc). There were additional features (eg. postaxial polydactyly) which were found in other affected and unaffected family members. Exome sequencing with autozygome analysis revealed homozygosity for a PLXNA2 stopgain variant (NM_025179:c.3603C>A / p.(Cys1201*)). Sanger confirmation was carried out and segregation analyses confirmed carrier status of the unaffected parents and a sib as well as a brother homozygous for the same variant. Clinical evaluation of the latter, following this finding revealed borderline intellectual functioning, ADHD, failure to thrive. There was no mandibular anomaly or overbite and no clinical evidence of CHD (no echo performed). The index patient from the 2nd consanguineous family was evaluated for ID (IQ of 63), with previous borderline motor development, ADHD and some dysmorphic features (obtuse mandibular angle and overbite). There was no clinical evidence of CHD (no echo performed). Exome sequencing with autozygosity mapping revealed a homozygous missense PLXNA2 variant (c.3073G>A / p.(Asp1025Asn), present only once in gnomAD (htz), with rather non-concordant in silico predictions SIFT 0.22, PolyPhen 0.682 and CADD 23.5. The aa was however highly conserved. Segregation analysis confirmed carrier state of the parents and 2 unaffected sibs, with a 3rd sib homozygous for the wt allele. As the authors discuss: *PLXNA2 belongs to the plexin family of genes, encoding transmbembrane proteins functioning as semaphorin receptors. It has predominant expression in neural tissue. The protein is thought to bind semaphorin-3A, -3C or -5 followed by plexin A2 dimerization, activation of its GTPase-activating protein domain, negative regulation of Rap1B GTPase and initiation of a signal transduction cascade mediating axonal repulsion/guidance, dendritic guidance, neuronal migration. *Murine Plxna2 knockout models display structural brain defects. In addition they display congenital heart defects incl. persistent truncus arteriosus and interrupted aortic arch. *Rare CNVs in adult humans with tetralogy of Fallot have suggested a potential role of PLXNA2 in cardiac development and CHD. *Expression and the role of PLXNA2 in human chondrocytes as well as a GWAS in 240 japanese patients with mandibular prognathism where PLXNA2 was suggested as a susceptibility locus. Overall, the authors recognize some common features (as for cognitive functioning, some dysmorphic features incl. obtuse mandibular angle and overbite in 2 unrelated subjects, failure to thrive 3/3) and provide plausible explanations for the variability / discordance of others eg: - Cyanotic heart disease explaining discordance in cognitive outcome among sibs - Incomplete penetrance for CHD (and/or ID or mandibular anomaly) as for few AR disorders and/or - Additional pathogenic variants possibly explaining the CHD in the first subject. There is no associated phenotype in OMIM or G2P. SysID includes PLXNA2 among the candidate ID genes. Sources: Literature |
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| Mendeliome v0.8823 | SLC51A |
Zornitza Stark gene: SLC51A was added gene: SLC51A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC51A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC51A were set to 31863603 Phenotypes for gene: SLC51A were set to Cholestasis, progressive familial intrahepatic, 6, MIM# 619484 Review for gene: SLC51A was set to RED Added comment: Single individual reported with homozygous LoF variant, who presented with chronic malabsorptive diarrhoea, easy bruising, episodes of prolonged bleeding that required blood transfusions, and failure to thrive. Laboratory testing at age 2.5 years showed elevated liver transaminases and alkaline phosphatase. Liver biopsy demonstrated portal and periportal fibrosis and hepatocytes with foci of hepatocytic cholestasis. Analysis of bile acids in a blood spot were normal. Treatment with ursodiol and cholestyramine was started at 5 years of age. The coagulopathy resolved and his growth was adequate, but his liver transaminases, direct bilirubin, and GGT levels remained elevated. Sources: Literature |
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| Mendeliome v0.8819 | MOCOS | Zornitza Stark Mode of inheritance for gene: MOCOS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8816 | HNMT | Zornitza Stark Mode of inheritance for gene: HNMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8813 | BLNK | Zornitza Stark Mode of inheritance for gene: BLNK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8810 | AICDA | Zornitza Stark Mode of inheritance for gene: AICDA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8807 | VPS50 |
Zornitza Stark gene: VPS50 was added gene: VPS50 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS50 were set to 34037727 Phenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum Review for gene: VPS50 was set to AMBER Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. Sources: Literature |
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| Mendeliome v0.8805 | SP6 | Zornitza Stark Mode of inheritance for gene: SP6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8803 | AMTN |
Zornitza Stark gene: AMTN was added gene: AMTN was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: AMTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AMTN were set to 27412008; 25715379; 26620968 Phenotypes for gene: AMTN were set to Amelogenesis imperfecta, type IIIB Mode of pathogenicity for gene: AMTN was set to Other Review for gene: AMTN was set to RED Added comment: In a Costa Rican family segregating autosomal dominant hypomineralized amelogenesis imperfecta, Smith et al. (2016) identified a heterozygous deletion/insertion mutation in the amelotin gene that segregated with the phenotype in the family. The mutation was predicted to result in an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 amino acids. Mode of pathogenicity not established. Toxic gain of function proposed as Atmn KO and +/- mice did not recapitulate the human phenotype. Sources: Expert Review |
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| Mendeliome v0.8800 | WDR72 | Zornitza Stark Mode of inheritance for gene: WDR72 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8797 | SLC24A4 | Zornitza Stark Mode of inheritance for gene: SLC24A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8794 | ROGDI | Zornitza Stark Mode of inheritance for gene: ROGDI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8792 | RELT |
Zornitza Stark gene: RELT was added gene: RELT was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: RELT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RELT were set to 30506946 Phenotypes for gene: RELT were set to Amelogenesis imperfecta, type IIIC, MIM# 618386 Review for gene: RELT was set to GREEN Added comment: Amelogenesis imperfecta type IIIC is characterized by hypocalcified enamel in both the primary and secondary dentition. The enamel is rough and yellow-brown; under normal use, the enamel disintegrates from occlusal surfaces of the molars, leaving a ring of intact enamel remaining on the sides. At least 3 families and a mouse model. Sources: Expert Review |
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| Mendeliome v0.8789 | LAMB3 | Zornitza Stark Mode of inheritance for gene: LAMB3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8782 | KLK4 | Zornitza Stark Mode of inheritance for gene: KLK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8780 | ITGB6 |
Zornitza Stark gene: ITGB6 was added gene: ITGB6 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ITGB6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITGB6 were set to 25431241; 26695873; 24305999; 24319098 Phenotypes for gene: ITGB6 were set to Amelogenesis imperfecta, type IH, MIM# 616221 Review for gene: ITGB6 was set to GREEN Added comment: At least 3 unrelated families reported. Sources: Expert Review |
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| Mendeliome v0.8777 | STAT3 | Zornitza Stark Mode of inheritance for gene: STAT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8774 | STK4 | Zornitza Stark Mode of inheritance for gene: STK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8773 | SP110 | Zornitza Stark Tag founder tag was added to gene: SP110. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8771 | SP110 | Zornitza Stark Mode of inheritance for gene: SP110 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8768 | SMARCAL1 | Zornitza Stark Mode of inheritance for gene: SMARCAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8765 | GPR68 | Zornitza Stark Mode of inheritance for gene: GPR68 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8762 | FAM83H | Zornitza Stark Mode of inheritance for gene: FAM83H was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8759 | ENAM | Zornitza Stark Mode of inheritance for gene: ENAM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8756 | FAM20A | Zornitza Stark Mode of inheritance for gene: FAM20A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8753 | C4orf26 | Zornitza Stark Mode of inheritance for gene: C4orf26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8750 | AMELX | Zornitza Stark Mode of inheritance for gene: AMELX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8749 | AMELX | Zornitza Stark Tag SV/CNV tag was added to gene: AMELX. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8747 | AMBN | Zornitza Stark Mode of inheritance for gene: AMBN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8741 | TCF7L2 |
Zornitza Stark changed review comment from: 2 reviews Konstantinos Varvagiannis (Other) I don't know Dias et al (2021 - PMID: 34003604) describe the phenotype of 11 unrelated individuals harboring de novo missense/truncating TCF7L2 variants. Features included DD in childhood (motor delay in 8/11, speech delay in 11/11), intellectual abilities ranging from average cognitive functioning to mild/moderate ID (the latter observed in 5/11), myopia (6/11) , dysmorphic features, variable orthopedic findings, and neuropsychiatric comorbidities incl. ASD (4/11) / ADHD (4/11). One additional (12th) individual was excluded from this summary due to concurrent diagnosis of hypoxic-ischemic injury. TCF7L2 on 10q25 encodes transcription factor 7-like 2, a high mobility group (HMG) box-containing transcription factor. As the authors discuss, the protein mediates canonical Wnt signaling. Secreted Wnt proteins lead to release of beta-catenin (CTNNB1) which after translocation to the nucleus acts with DNA-binding factors incl. TCF7L2 to turn on Wnt-responsive target genes. As a result TCF7L2 acts with beta-catenin as a switch for transcriptional regulation. Multiple alternative spliced TCF7L2 transcripts mediate it's function and specificity of transcriptional repertoire in a variety of tissues and contexts. Dias et al provide references for its role in nervous system development incl. neurogenesis and thalamic development. Variants in all cases occurred as de novo events with pLoF (stopgain, frameshift, splicing) ones predicted to lead to NMD. Missense variants occurred in all cases in or adjacent to the HMG box domain [aa 350-417]. 5 different missense variants affecting 3 residues were reported incl. c.1142A>C, c.1143C>G (leading to Asn381Thr/Lys respectively), c.1250G>T (Trp417Leu), c.1267T>C, c.1268A>G (leading to Tyr423His/Cys) [NM_001146274.1]. The gene has a pLI of 0.99-1 gnomAD/ExAC while there is a region of missense constraint encompassing the HMG box domain (the latter is an evolutionary conserved region mediating interactions with DNA). No phenotypic differences were observed among individuals with pLoF and missense SNVs, and haploinsufficiency is presumed to be the underlying mechanism. There are no variant or other studies performed, nor any animal models discussed. In supplementary table 2, the authors provide several references to previous large scale sequencing studies with brief/incomplete descriptions of individuals de novo TCF7L2 variants and neurodevelopmental disorder (ID/ASD - Iossifov, De Rubeis, Lelieveld, McRae/DDD study and many other Refs). Heterozygous TCF7L2 variants are thought to confer susceptibility to type diabetes mellitus (MIM 125853). Individuals reported by Dias et al did not have endocrine abnormalities including DM. A study by Roychowdhury et al (2021 - PMID: 34265237) suggests that regulatory variants in TCF7L2 are associated with thoracic aneurysm. There is no other associated phenotype (notably NDD) in OMIM. G2P includes TCF7L2 in its DD panel (Disease : TC7L2-related DD, Confidence:confirmed, Monoallelic, LoF). SysID includes this gene within the autism candidate genes and current primary ID genes.; to: Dias et al (2021 - PMID: 34003604) describe the phenotype of 11 unrelated individuals harboring de novo missense/truncating TCF7L2 variants. Features included DD in childhood (motor delay in 8/11, speech delay in 11/11), intellectual abilities ranging from average cognitive functioning to mild/moderate ID (the latter observed in 5/11), myopia (6/11) , dysmorphic features, variable orthopedic findings, and neuropsychiatric comorbidities incl. ASD (4/11) / ADHD (4/11). One additional (12th) individual was excluded from this summary due to concurrent diagnosis of hypoxic-ischemic injury. TCF7L2 on 10q25 encodes transcription factor 7-like 2, a high mobility group (HMG) box-containing transcription factor. As the authors discuss, the protein mediates canonical Wnt signaling. Secreted Wnt proteins lead to release of beta-catenin (CTNNB1) which after translocation to the nucleus acts with DNA-binding factors incl. TCF7L2 to turn on Wnt-responsive target genes. As a result TCF7L2 acts with beta-catenin as a switch for transcriptional regulation. Multiple alternative spliced TCF7L2 transcripts mediate it's function and specificity of transcriptional repertoire in a variety of tissues and contexts. Dias et al provide references for its role in nervous system development incl. neurogenesis and thalamic development. Variants in all cases occurred as de novo events with pLoF (stopgain, frameshift, splicing) ones predicted to lead to NMD. Missense variants occurred in all cases in or adjacent to the HMG box domain [aa 350-417]. 5 different missense variants affecting 3 residues were reported incl. c.1142A>C, c.1143C>G (leading to Asn381Thr/Lys respectively), c.1250G>T (Trp417Leu), c.1267T>C, c.1268A>G (leading to Tyr423His/Cys) [NM_001146274.1]. The gene has a pLI of 0.99-1 gnomAD/ExAC while there is a region of missense constraint encompassing the HMG box domain (the latter is an evolutionary conserved region mediating interactions with DNA). No phenotypic differences were observed among individuals with pLoF and missense SNVs, and haploinsufficiency is presumed to be the underlying mechanism. There are no variant or other studies performed, nor any animal models discussed. In supplementary table 2, the authors provide several references to previous large scale sequencing studies with brief/incomplete descriptions of individuals de novo TCF7L2 variants and neurodevelopmental disorder (ID/ASD - Iossifov, De Rubeis, Lelieveld, McRae/DDD study and many other Refs). Heterozygous TCF7L2 variants are thought to confer susceptibility to type diabetes mellitus (MIM 125853). Individuals reported by Dias et al did not have endocrine abnormalities including DM. A study by Roychowdhury et al (2021 - PMID: 34265237) suggests that regulatory variants in TCF7L2 are associated with thoracic aneurysm. There is no other associated phenotype (notably NDD) in OMIM. G2P includes TCF7L2 in its DD panel (Disease : TC7L2-related DD, Confidence:confirmed, Monoallelic, LoF). SysID includes this gene within the autism candidate genes and current primary ID genes. |
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| Mendeliome v0.8739 | LTBP3 | Zornitza Stark Mode of inheritance for gene: LTBP3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8738 | ARIH1 | Zornitza Stark Mode of inheritance for gene: ARIH1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8736 | PIDD1 |
Zornitza Stark gene: PIDD1 was added gene: PIDD1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIDD1 were set to 28397838; 29302074; 33414379; 34163010 Phenotypes for gene: PIDD1 were set to Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum Review for gene: PIDD1 was set to GREEN Added comment: There is enough evidence to include this gene in the current panel with green rating. Biallelic PIDD1 pathogenic variants have been reported in 26 individuals (11 families) with DD (all), variable degrees of ID (mild to severe), behavioral (eg. aggression/self-mutilation in several, ADHD) and/or psychiatric abnormalities (ASD, psychosis in 5 belonging to 3 families), well-controlled epilepsy is some (9 subjects from 6 families) and MRI abnormalities notably abnormal gyration pattern (pachygyria with predominant anterior gradient) as well as corpus callosum anomalies (commonly thinning) in several. Dysmorphic features have been reported in almost all, although there has been no specific feature suggested. The first reports on the phenotype associated with biallelic PIDD1 mutations were made by Harripaul et al (2018 - PMID: 28397838) and Hu et al (2019 - PMID: 29302074) [both studies investigating large cohorts of individuals with ID from consanguineous families]. Sheikh et al (2021 - PMID: 33414379) provided details on the phenotype of 15 individuals from 5 families including those from the previous 2 reports and studied provided evidence on the role of PIDD1 and the effect of variants. Zaki et al (2021 - PMID: 34163010) reported 11 additional individuals from 6 consanguineous families, summarize the features of all subjects published in the literature and review the neuroradiological features of the disorder. PIDD1 encodes p53-induced death domain protein 1. The protein is part of the PIDDosome, a multiprotein complex also composed of the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 and induces apoptosis in response to DNA damage. There are 5 potential PIDD1 mRNA transcript variants with NM_145886.4 corresponding to the longest. Similar to the protein encoded by CRADD, PIDD1 contains a death domain (DD - aa 774-893). Constitutive post-translational processing gives PIDD1-N, PIDD1-C the latter further processed into PIDD1-CC (by auto-cleavage). Serine residues at pos. 446 and 588 are involved in this autoprocessing generating PIDD1-C (aa 446-910) and PIDD1-CC (aa 774-893). The latter is needed for caspase-2 activation. Most (if not all) individuals belonged to consanguineous families of different origins and harbored pLoF or missense variants. Variants reported so far include : c.2587C>T; p.Gln863* / c.1909C>T ; p.Arg637* / c.2443C>T / p.Arg815Trp / c.2275-1G>A which upon trap assay was shown to lead to skipping of ex15 with direct splicing form exon14 to the terminal exon 16 (resulting to p.Arg759Glyfs*1 with exlcusion of the entire DD) / c.2584C>T; p.Arg862Trp / c.1340G>A; p.Trp447* / c.2116_2120del; p.Val706His*, c.1564_1565del; p.Gly602fs*26 Evidence so far provided includes: - Biallelic CRADD variants cause a NDD disorder and a highly similar gyration pattern. - Confirmation of splicing effect (eg. for c.2275-1G>A premature stop in position 760) or poor expression (NM_145886.3:c.2587C>T; p.Gln863*). Arg815Trp did not affect autoprocessing or protein stability. - Abnormal localization pattern, loss of interaction with CRADD and failure to activate caspase-2 (MDM2 cleavage assay) [p.Gln863* and Arg815Trp] - Available expression data from GTEx (PIDD1 having broad expression in multiple tissues, but higher in brain cerebellum) as well as BrainSpan and PsychEncode studies suggesting high coexpression of PIDD1, CRADD and CASP2 in many regions in the developing human brain. - Variants in other genes encoding proteins interacting with PIDD1 (MADD, FADD, DNAJ, etc) are associated with NDD. Pidd-1 ko mice (ex3-15 removal) lack however CNS-related phenotypes. These show decreased anxiety but no motor anomalies. This has also been the case with Cradd-/- mice displaying no significant CNS phenotypes without lamination defects. There is currently no associated phenotype in OMIM. PIDD1 is listed in the DD panel of G2P (PIDD1-related NDD / biallelic / loss of function / probable) . SysID includes PIDD1 among the current primary ID genes. Sources: Expert Review |
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| Mendeliome v0.8734 | COLGALT1 |
Bryony Thompson gene: COLGALT1 was added gene: COLGALT1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980 Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3 MIM#618360 Review for gene: COLGALT1 was set to GREEN Added comment: 3 unrelated cases with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos. Sources: Other |
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| Mendeliome v0.8732 | JAKMIP1 |
Seb Lunke gene: JAKMIP1 was added gene: JAKMIP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: JAKMIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: JAKMIP1 were set to 29158550; 26627310; 27799067 Phenotypes for gene: JAKMIP1 were set to Intellectual disability; Seizures Review for gene: JAKMIP1 was set to AMBER Added comment: Identified in two independent patients in the literature with a mouse model. Patient 1 (27799067) with developmental delay, speech delay, and cognitive impairment; self-injurious and aggressive behaviour, seizures, dysmorphic features. De-novo missense JAKMIP1 (p.D586H). Patient 2 (29158550) with feeding difficulties, hypotonia, epilepsy, severe ID, no active speech, kyphoscoliosis, constipation, autism, short stature. Splice variant c.1432-2A>G, no segregation or RNA data available. KO mouse model (27799067) displays social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors. Sources: Literature |
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| Mendeliome v0.8730 | ARIH1 |
Bryony Thompson gene: ARIH1 was added gene: ARIH1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: ARIH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARIH1 were set to 29689197; 32102558 Phenotypes for gene: ARIH1 were set to Thoracic aortic aneurysm Review for gene: ARIH1 was set to GREEN Added comment: 3 unrelated families: A de novo case (R171*) with thoracic aortic aneurysm (TAA), and 2 siblings with TAA and a missense (E15Q). Another proband with cerebrovascular aneurysm (family history of TAA) and a missense variant (E44G). Supporting functional assays of the variants and a drosophila model. Sources: Other |
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| Mendeliome v0.8726 | PRPF31 | Zornitza Stark Mode of inheritance for gene: PRPF31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8725 | PRPF31 | Zornitza Stark Tag SV/CNV tag was added to gene: PRPF31. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8723 | RNF168 | Zornitza Stark Mode of inheritance for gene: RNF168 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8720 | RFXAP | Zornitza Stark Mode of inheritance for gene: RFXAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8719 | RFXAP | Zornitza Stark Tag founder tag was added to gene: RFXAP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8717 | RFXANK | Zornitza Stark Tag founder tag was added to gene: RFXANK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8717 | RFXANK | Zornitza Stark Mode of inheritance for gene: RFXANK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8714 | RBCK1 | Zornitza Stark Mode of inheritance for gene: RBCK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8712 | ABCC2 | Zornitza Stark Mode of inheritance for gene: ABCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8707 | UBR1 | Zornitza Stark Mode of inheritance for gene: UBR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8704 | ACTL6A | Zornitza Stark Mode of inheritance for gene: ACTL6A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8703 | VAV1 |
Zornitza Stark gene: VAV1 was added gene: VAV1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: VAV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VAV1 were set to 20638113; 23058036 Phenotypes for gene: VAV1 were set to Common variable immnodeficiency Review for gene: VAV1 was set to RED Added comment: Reduced VAV1 expression has been reported in multiple T-CVID cases, however only one large deletion (exon 2-27) has been reported in a single case in a publication from 2012. The CNV was detected using real-time qPCR, but was not confirmed by an orthogonal method. Sources: Expert Review |
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| Mendeliome v0.8700 | TCF3 | Zornitza Stark Mode of inheritance for gene: TCF3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8697 | PRKCD | Zornitza Stark Mode of inheritance for gene: PRKCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8694 | CD19 | Zornitza Stark Mode of inheritance for gene: CD19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8691 | SNRPB | Zornitza Stark Mode of inheritance for gene: SNRPB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8690 | SNRPB |
Zornitza Stark Tag 5'UTR tag was added to gene: SNRPB. Tag deep intronic tag was added to gene: SNRPB. |
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| Mendeliome v0.8688 | RBM10 | Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8684 | POLR1D | Zornitza Stark Mode of inheritance for gene: POLR1D was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8679 | POLR1C | Zornitza Stark Mode of inheritance for gene: POLR1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8676 | SF3B4 | Zornitza Stark Mode of inheritance for gene: SF3B4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8673 | TMCO1 | Zornitza Stark Mode of inheritance for gene: TMCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8671 | RGS10 |
Zornitza Stark gene: RGS10 was added gene: RGS10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RGS10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RGS10 were set to 34315806; 34339853 Phenotypes for gene: RGS10 were set to Immunodeficiency; short stature Review for gene: RGS10 was set to RED Added comment: Three affected siblings with short stature and immunodeficiency and segregating biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals had recurrent infections, hypergammaglobulinaemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Limited functional data presented. Further experimental data linking RGS10 to immune function presented in PMID 34339853. Sources: Literature |
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| Mendeliome v0.8669 | MAST3 |
Zornitza Stark gene: MAST3 was added gene: MAST3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAST3 were set to 34185323 Phenotypes for gene: MAST3 were set to Developmental and epileptic encephalopathy Review for gene: MAST3 was set to GREEN Added comment: Eleven individuals reported with de novo missense variants in the STK domain, including two recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at <2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. Limited functional data. Sources: Literature |
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| Mendeliome v0.8667 | SF3B2 |
Zornitza Stark gene: SF3B2 was added gene: SF3B2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SF3B2 were set to 34344887 Phenotypes for gene: SF3B2 were set to Craniofacial microsomia Review for gene: SF3B2 was set to GREEN Added comment: Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities. Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease. The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases. Sources: Literature |
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| Mendeliome v0.8664 | IMPG1 | Zornitza Stark Mode of inheritance for gene: IMPG1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8659 | CUL7 | Zornitza Stark Mode of inheritance for gene: CUL7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8656 | NFKBIA | Zornitza Stark Mode of pathogenicity for gene: NFKBIA was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8655 | NFKBIA | Zornitza Stark Mode of inheritance for gene: NFKBIA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8652 | NFKB2 | Zornitza Stark Mode of inheritance for gene: NFKB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8649 | NFKB1 | Zornitza Stark Mode of inheritance for gene: NFKB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8646 | MCM4 | Zornitza Stark Mode of inheritance for gene: MCM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8644 | MCM4 | Zornitza Stark Tag founder tag was added to gene: MCM4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8642 | MAP3K14 | Zornitza Stark Mode of inheritance for gene: MAP3K14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8639 | LRBA | Zornitza Stark Mode of inheritance for gene: LRBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8636 | AQP2 | Zornitza Stark Mode of inheritance for gene: AQP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8632 | GIMAP5 |
Zornitza Stark gene: GIMAP5 was added gene: GIMAP5 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GIMAP5 were set to 33956074 Phenotypes for gene: GIMAP5 were set to Portal hypertension, noncirrhotic, 2, MIM# 619463 Review for gene: GIMAP5 was set to GREEN Added comment: 8 individuals from 4 unrelated families reported with onset of disease in the first decade of life. Clinical features included jaundice, hyperbilirubinaemia, pancytopaenia, including neutropaenia, lymphopaenia, and thrombocytopaenia, hepatosplenomegaly, and oesophageal varices. Some individuals had recurrent infections or features suggestive of an immunodeficiency. Liver biopsy was notable for the absence of cirrhosis and the presence of nodular regeneration. Sources: Expert list |
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| Mendeliome v0.8627 | IL7R | Zornitza Stark Mode of inheritance for gene: IL7R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8624 | MALT1 | Zornitza Stark Mode of inheritance for gene: MALT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8621 | IL2RG | Zornitza Stark Mode of inheritance for gene: IL2RG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8618 | IKZF1 | Zornitza Stark Mode of inheritance for gene: IKZF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8615 | ITK | Zornitza Stark Mode of inheritance for gene: ITK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8612 | PLCB4 | Zornitza Stark Mode of inheritance for gene: PLCB4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8609 | PBX1 | Zornitza Stark Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8606 | VRK1 |
Zornitza Stark changed review comment from: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.; to: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia. Further delineation of phenotype 2021: PMID 34169149: expanding spectrum of neurologic disorders associated with VRK1. Two Hispanic individuals, one homozygous (R321C: VUS and LP/P in ClinVar) and one cHet (R321C+V236M, latter P and more recently VUS in ClinVar), with slowly progressive weakness and a clinical syndrome consistent with adult-onset spinal muscular atrophy WITHOUT pontocerebellar atrophy. No hom in gnomAD and both have been reported in cHet individuals with other features: R321C in association with adult-onset amyotrophic lateral sclerosis and V236M with rapidly progressive sensorimotor polyneuropathy and microcephaly. Authors suggest PMID 26583493 and 31837156 have similar reports. PMID 26583493 reports a 32yo Hispanic individual, cHet H119R+R321C, with early-onset amyotrophic lateral sclerosis, 5 years progressive weakness. PMID 31837156 reports two patients with adult-onset length-dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent, both hom for R387H. |
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| Mendeliome v0.8606 | CLCN3 | Zornitza Stark Mode of inheritance for gene: CLCN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8601 | CLCN3 |
Kristin Rigbye gene: CLCN3 was added gene: CLCN3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CLCN3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CLCN3 were set to PMID: 34186028 Phenotypes for gene: CLCN3 were set to Neurodevelopmental disorder Mode of pathogenicity for gene: CLCN3 was set to Other Review for gene: CLCN3 was set to GREEN Added comment: 11 individuals reported, 9 that carried 8 different rare heterozygous missense variants in CLCN3, and 2 siblings that were homozygous for an NMD-predicted frameshift variant likely abolishing ClC-3 function. All missense variants were confirmed to be de novo in eight individuals for whom parental data was available. The 11 individuals in the cohort share clinical features of variable severity. All 11 have GDD or ID and dysmorphic features, and a majority has mood or behavioural disorders and structural brain abnormalities: - Structural brain abnormalities on MRI (9/11) included partial or full agenesis of the corpus callosum (6/9), disorganized cerebellar folia (4/9), delayed myelination (3/9), decreased white matter volume (3/9), pons hypoplasia (3/9), and dysmorphic dentate nuclei (3/9). Six of those with brain abnormalities also presented with seizures. - Nine have abnormal vision, including strabismus in four and inability to fix or follow in the two with homozygous loss-of-function variants. - Hypotonia ranging from mild to severe was reported in 7 of the 11 individuals. - Six have mood or behavioural disorders, particularly anxiety (3/6). - Consistent dysmorphic facial features included microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia. The severity of disease in the two siblings with homozygous disruption of ClC-3 is consistent with the drastic phenotype seen in Clcn3 KO mice. The disease was more severe in two siblings carrying homozygous loss-of-function variants with the presence of GDD, absent speech, seizures, and salt and pepper fundal pigmentation in both individuals, with one deceased at 14 months of age. The siblings also had significant neuroanatomical findings including diffusely decreased white matter volume, thin corpora callosa, small hippocampi, and disorganized cerebellar folia. Supporting biallelic inheritance for LoF variants, disruption of mouse Clcn3 results in drastic neurodegeneration with loss of the hippocampus a few months after birth and early retinal degeneration. Clcn3−/− mice display severe neurodegeneration, whereas heterozygous Clcn3+/− mice appear normal. Patch-clamp studies were used to investigate four of the missense variants. These suggested a gain of function in two variants with increased current in HEK cells, however they also showed reduced rectification of voltage and a loss of transient current, plus decreased current amplitude, glycosylation and surface expression when expressed in oocytes, and were suspected to interfere with channel gating and a negative feedback mechanism. These effects were also shown to vary depending on pH levels. The current of the remaining two variants did not differ from WT. For heterozygous missense variants, the disruption induced may be at least partially conferred to mutant/WT homodimers and mutant/ClC-4 heterodimers. Both loss and gain of function in this gene resulted in the same phenotype. Sources: Literature |
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| Mendeliome v0.8601 | TNPO2 |
Elena Savva gene: TNPO2 was added gene: TNPO2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TNPO2 were set to PMID: 34314705 Phenotypes for gene: TNPO2 were set to Developmental delays, neurologic deficits and dysmorphic features Mode of pathogenicity for gene: TNPO2 was set to Other Review for gene: TNPO2 was set to GREEN Added comment: PMID: 34314705 - all de novo missense variants with intellectual disability (9/9), speech impairment (15/15), motor impairment (15/15), ophthalmologic abnormalities (10/15), muscle tone abnormalities (11/15, primarily hypotonia), seizures (6/15, febrile to non-febrile), microcephaly (5/15) and MRI anomalies (7/13, 3/13 had cerebellar hypoplasia/dysplasia). Null fly model was homozygous lethal, no obvious phenotypes in heterozygotes. Upregulated gene expression also resulted in lethality. Overexpression of some human variants in fly models resulted in "toxicity" and phenotypic defects, authors speculate two variants are GOF, 1 variant is LOF. gnomAD: minimal PTCs present Sources: Literature |
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| Mendeliome v0.8601 | DNAH10 |
Ain Roesley gene: DNAH10 was added gene: DNAH10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAH10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH10 were set to 34237282 Phenotypes for gene: DNAH10 were set to primary male infertility with asthenoteratozoospermia Penetrance for gene: DNAH10 were set to unknown Review for gene: DNAH10 was set to GREEN Added comment: 4x families with 5 affecteds (chets and homs - 4 missense and 2 fs). Knockout mouse models were infertile and showed significant reduction in count and motility compared to heterozygous mice Sources: Literature |
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| Mendeliome v0.8600 | AP1G1 |
Danielle Ariti gene: AP1G1 was added gene: AP1G1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AP1G1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: AP1G1 were set to 34102099 Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy Mode of pathogenicity for gene: AP1G1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: AP1G1 was set to GREEN Added comment: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants. Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site. Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality. All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe. Sources: Literature |
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| Mendeliome v0.8598 | SPTBN1 |
Belinda Chong changed review comment from: PMID: 34211179 - Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. - Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. PMID: 33847457 - Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset. - identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities). - Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis. Sources: Literature; to: PMID: 34211179 - Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures (9/29); behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. - Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. PMID: 33847457 - Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset. - identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities). - Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis. Sources: Literature |
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| Mendeliome v0.8596 | SPTBN4 | Zornitza Stark Mode of inheritance for gene: SPTBN4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8586 | SEMA3D |
Ain Roesley gene: SEMA3D was added gene: SEMA3D was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEMA3D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SEMA3D were set to 34159400 Penetrance for gene: SEMA3D were set to unknown Review for gene: SEMA3D was set to RED Added comment: 1x de novo missense in a proband with short stature, absent distal phalanges of the 5th fingers and toes, and dysplastic middle phalanges of the toes. However, there is 4 hets in gnomAD v2 Sources: Literature |
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| Mendeliome v0.8586 | HMGB1 |
Ain Roesley gene: HMGB1 was added gene: HMGB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HMGB1 were set to 34159400 Phenotypes for gene: HMGB1 were set to Mirror image foot polydactyly Penetrance for gene: HMGB1 were set to unknown Review for gene: HMGB1 was set to RED Added comment: 1x de novo fs, no functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development Sources: Literature |
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| Mendeliome v0.8586 | SPTBN1 |
Belinda Chong gene: SPTBN1 was added gene: SPTBN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SPTBN1 were set to PMID: 34211179; PMID: 33847457 Phenotypes for gene: SPTBN1 were set to Neurodevelopmental Syndrome Review for gene: SPTBN1 was set to GREEN Added comment: PMID: 34211179 - Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. - Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. PMID: 33847457 - Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset. - identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities). - Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis. Sources: Literature |
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| Mendeliome v0.8586 | EDEM3 |
Michelle Torres gene: EDEM3 was added gene: EDEM3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EDEM3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EDEM3 were set to 34143952 Phenotypes for gene: EDEM3 were set to EDEM3-congenital disorder of glycosylation Review for gene: EDEM3 was set to GREEN Added comment: PMID: 34143952: 7 families (11 individuals) with 6x PTV and 2x missense variants with neurodevelopmental delay and variable facial dysmorphisms. The unaffected parents were all heterozygous carriers. Functional show LoF of EDEM3 enzymatic activity. Sources: Literature |
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| Mendeliome v0.8586 | GCNA |
Ain Roesley gene: GCNA was added gene: GCNA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GCNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: GCNA were set to 33963445 Phenotypes for gene: GCNA were set to primary spermatogenic failure Penetrance for gene: GCNA were set to unknown Review for gene: GCNA was set to GREEN Added comment: 7x probands all missense except 1 fs. Variants had <0.0005 MAF in gnomad v2 male cohort and absent in 5784 Dutch control cohort no functional studies were done except for histology of Ser659Trp, revealing a Sertoli-cell only Sources: Literature |
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| Mendeliome v0.8585 | ANK2 |
Zornitza Stark gene: ANK2 was added gene: ANK2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ANK2 were set to 31983240; 22542183; 25363768; 27479843; 28554332; 30564305; 30755392; 31981491; 33004838; 33057194 Phenotypes for gene: ANK2 were set to Long QT syndrome 4, MIM# 600919; Complex neurodevelopmental disorder, MONDO:0100038 Review for gene: ANK2 was set to GREEN Added comment: Link with cardiac abnormalities such as LongQT is DISPUTED. More than 10 unrelated individuals reported with neurodevelopmental phenotype, comprising autism/ID and de novo truncating variants, in addition to many other individuals as part of large NDD cohorts. This association has been assessed as DEFINITIVE by ClinGen. Sources: Expert Review |
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| Mendeliome v0.8583 | PRDX3 |
Hazel Phillimore changed review comment from: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex. Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres. The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism. The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense. Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated. Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species. In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress. Sources: Literature; to: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex. Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres. The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism. The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense. Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated. Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species. In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress. Sources: Literature |
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| Mendeliome v0.8583 | PRDX3 |
Hazel Phillimore gene: PRDX3 was added gene: PRDX3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRDX3 were set to PMID: 33889951 Phenotypes for gene: PRDX3 were set to cerebellar ataxia (early onset, mild to moderate, progressive) Penetrance for gene: PRDX3 were set to unknown Review for gene: PRDX3 was set to GREEN Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex. Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres. The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism. The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense. Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated. Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species. In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress. Sources: Literature |
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| Mendeliome v0.8581 | GSC | Zornitza Stark Mode of inheritance for gene: GSC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8578 | GNAI3 | Zornitza Stark Mode of inheritance for gene: GNAI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8575 | EIF4A3 | Zornitza Stark Mode of inheritance for gene: EIF4A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8570 | PDCL3 |
Zornitza Stark gene: PDCL3 was added gene: PDCL3 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: PDCL3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDCL3 were set to 32621347 Phenotypes for gene: PDCL3 were set to Megacystis-microcolon Review for gene: PDCL3 was set to AMBER Added comment: Single publication (PMID 32621347): one family with two affected fetuses - one with megacystis and microcolon, and the other with megacystisis and bilateral diaphragmatic hernia (prune-belly phenotype). Compound het LOF variants in PDCL3 (one frameshift and one missense). Complete absence of PDLC3 expression demonstrated in one of the affected fetuses. No homozygous LOF PDCL3 variants in gnomAD. PCDL3 negatively modulates actin folding and is strongly expressed in smooth muscle of bladder and colon. Sources: Expert Review |
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| Mendeliome v0.8567 | SGO1 | Zornitza Stark Mode of inheritance for gene: SGO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8563 | TYMP | Zornitza Stark Mode of inheritance for gene: TYMP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8560 | ZNF687 | Zornitza Stark Mode of inheritance for gene: ZNF687 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8559 | ZNF687 | Zornitza Stark Tag founder tag was added to gene: ZNF687. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8557 | GRHPR | Zornitza Stark Mode of inheritance for gene: GRHPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8554 | AGXT | Zornitza Stark Mode of inheritance for gene: AGXT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8551 | HOGA1 | Zornitza Stark Mode of inheritance for gene: HOGA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8548 | VPS45 | Zornitza Stark Mode of inheritance for gene: VPS45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8545 | LAMTOR2 | Zornitza Stark Mode of inheritance for gene: LAMTOR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8542 | IKZF3 |
Zornitza Stark gene: IKZF3 was added gene: IKZF3 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: IKZF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IKZF3 were set to 34155405 Phenotypes for gene: IKZF3 were set to Immunodeficiency 84, MIM# 619437 Review for gene: IKZF3 was set to AMBER Added comment: Single family reported where heterozygous missense variant in this gene segregated with immunodeficiency in a mother and two children. Findings included low levels of B cells and impaired early B-cell development, variable T-cell abnormalities, hypogammaglobulinaemia, increased susceptibility to infection with Epstein-Barr virus (EBV). One individual developed lymphoma in adulthood. Mouse model recapitulated phenotype. Sources: Expert Review |
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| Mendeliome v0.8539 | HSD17B4 | Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8536 | LCK | Zornitza Stark Mode of inheritance for gene: LCK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8531 | DOCK8 | Zornitza Stark Mode of inheritance for gene: DOCK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8528 | DOCK2 | Zornitza Stark Mode of inheritance for gene: DOCK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8525 | DNMT3B | Zornitza Stark Mode of inheritance for gene: DNMT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8522 | SYNCRIP |
Zornitza Stark gene: SYNCRIP was added gene: SYNCRIP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937 Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology Review for gene: SYNCRIP was set to GREEN Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases. Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals. The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence. Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance. Overall the variants reported to date include [NM_006372.5]: 1 - c.858_859del p.(Gly287Leufs*5) 2 - c.854dupA p.(Asn285Lysfs*8) 3 - c.734T>C p.(Leu245Pro) 4 - chr6:85605276-85683190 deletion (GRCh38) 5 - c.629T>C p.(Phe210Ser) 6 - c.1573_1574delinsTT p.(Gln525Leu) 7 - c.1247_1250del p.(Arg416Lysfs*145) 8 - c.1518_1519insC p.(Ala507Argfs*14) [P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1] SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation. Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD. The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2. There are no additional studies performed. Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%] Animal models are not discussed. There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes. Sources: Literature |
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| Mendeliome v0.8519 | MSN | Zornitza Stark Mode of inheritance for gene: MSN was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8516 | JAGN1 | Zornitza Stark Mode of inheritance for gene: JAGN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8513 | ITGB2 | Zornitza Stark Mode of inheritance for gene: ITGB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8511 | CAMK4 |
Zornitza Stark gene: CAMK4 was added gene: CAMK4 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350 Phenotypes for gene: CAMK4 were set to Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus Review for gene: CAMK4 was set to GREEN Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant. Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms. CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018). The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below]. Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function. Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported. Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below). Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function. Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID. --- The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy. Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one. Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein. Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect. To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV. Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect. ---- Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20]. ---- Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*). Sources: Expert Review |
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| Mendeliome v0.8508 | FERMT3 | Zornitza Stark Mode of inheritance for gene: FERMT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8504 | CYBB | Zornitza Stark Mode of inheritance for gene: CYBB was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8500 | CSF3R | Zornitza Stark Mode of inheritance for gene: CSF3R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8493 | CEBPE | Zornitza Stark Mode of inheritance for gene: CEBPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8490 | NCF1 | Zornitza Stark Mode of inheritance for gene: NCF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8482 | C1QA | Zornitza Stark Mode of inheritance for gene: C1QA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8479 | CIITA | Zornitza Stark Mode of inheritance for gene: CIITA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8476 | CD40LG | Zornitza Stark Mode of inheritance for gene: CD40LG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8473 | CD3G | Zornitza Stark Mode of inheritance for gene: CD3G was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8472 | WDR26 | Zornitza Stark Mode of inheritance for gene: WDR26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8465 | ABCD4 | Zornitza Stark Mode of inheritance for gene: ABCD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8463 | ABCD1 | Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8458 | CCBE1 | Zornitza Stark Mode of inheritance for gene: CCBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8455 | CD27 | Zornitza Stark Mode of inheritance for gene: CD27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8450 | PCLO | Zornitza Stark Mode of inheritance for gene: PCLO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8449 | ZNF148 |
Natalie Tan gene: ZNF148 was added gene: ZNF148 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF148 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZNF148 were set to PMID: 27964749 Phenotypes for gene: ZNF148 were set to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; MIM#617260 Review for gene: ZNF148 was set to GREEN Added comment: Four unrelated individuals with de novo heterozygous nonsense or frameshift mutations (all resulting in premature termination codons in the last exon of ZNF148, predicted to escape nonsense-mediated mRNA decay and result in expression of a truncated protein). Phenotype characterised by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. No functional studies to date. Sources: Literature |
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| Mendeliome v0.8449 | RAC3 |
Natalie Tan gene: RAC3 was added gene: RAC3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAC3 were set to PMID: 30293988; 29276006 Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577 Review for gene: RAC3 was set to GREEN Added comment: Multiple unrelated individuals with heterozygous missense variants and a concordant phenotype (severe intellectual disability with brain malformations). No functional studies to date. Sources: Literature |
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| Mendeliome v0.8447 | CHRNA4 | Zornitza Stark Mode of pathogenicity for gene: CHRNA4 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8446 | CHRNA4 | Zornitza Stark Mode of inheritance for gene: CHRNA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8443 | ZIC3 | Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8441 | VPS13B | Zornitza Stark Mode of inheritance for gene: VPS13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8438 | TULP1 | Zornitza Stark Mode of inheritance for gene: TULP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8435 | TOPORS | Zornitza Stark Mode of inheritance for gene: TOPORS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8432 | SUFU | Zornitza Stark Mode of inheritance for gene: SUFU was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8429 | SCNN1G | Zornitza Stark Mode of inheritance for gene: SCNN1G was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8426 | SCLT1 | Zornitza Stark Mode of inheritance for gene: SCLT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8423 | RPGR | Zornitza Stark Mode of inheritance for gene: RPGR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8420 | PRKCSH | Zornitza Stark Mode of pathogenicity for gene: PRKCSH was changed from to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8419 | PRKCSH | Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8416 | POC1B | Zornitza Stark Mode of inheritance for gene: POC1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8413 | PMM2 | Zornitza Stark Mode of inheritance for gene: PMM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8411 | PKHD1 | Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8408 | MUC1 | Zornitza Stark Mode of inheritance for gene: MUC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8405 | KIF7 | Zornitza Stark Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8402 | KIAA0753 | Zornitza Stark Mode of inheritance for gene: KIAA0753 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8399 | KIAA0586 | Zornitza Stark Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8396 | IFT52 | Zornitza Stark Mode of inheritance for gene: IFT52 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8393 | IFT27 | Zornitza Stark Mode of inheritance for gene: IFT27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8390 | POLG2 | Zornitza Stark Mode of inheritance for gene: POLG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8388 | PCDHGC4 |
Zornitza Stark gene: PCDHGC4 was added gene: PCDHGC4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PCDHGC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCDHGC4 were set to 34244665 Phenotypes for gene: PCDHGC4 were set to Intellectual disability; Seizures Review for gene: PCDHGC4 was set to GREEN Added comment: Eight variants reported in 19 members of nine unreleted families with a neurodevelopmental syndrome. Severe or moderate intellectual disabilty in eight families and seizures in four families. Four of the variants were LoF, in silico analysis of the remaining missense (n=3) and splice variants were predicted to be pathogenic. Sources: Literature |
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| Mendeliome v0.8385 | ATP6V0A4 | Zornitza Stark Mode of inheritance for gene: ATP6V0A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8382 | ICK | Zornitza Stark Mode of inheritance for gene: ICK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8381 | HNF1B | Zornitza Stark Tag SV/CNV tag was added to gene: HNF1B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8380 | HNF1B | Zornitza Stark Mode of inheritance for gene: HNF1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8377 | GDF1 | Zornitza Stark Mode of inheritance for gene: GDF1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8374 | EVC2 | Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8371 | EVC | Zornitza Stark Mode of inheritance for gene: EVC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8368 | DCDC2 | Zornitza Stark Mode of inheritance for gene: DCDC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8365 | CRELD1 | Zornitza Stark Mode of inheritance for gene: CRELD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8362 | CRB2 | Zornitza Stark Mode of inheritance for gene: CRB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8359 | CEP55 | Zornitza Stark Mode of inheritance for gene: CEP55 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8356 | CENPF | Zornitza Stark Mode of inheritance for gene: CENPF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8353 | C8orf37 | Zornitza Stark Mode of inheritance for gene: C8orf37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8350 | C2CD3 | Zornitza Stark Mode of inheritance for gene: C2CD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8346 | CHRM3 | Zornitza Stark Mode of inheritance for gene: CHRM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8345 | ARHGAP42 |
Zornitza Stark gene: ARHGAP42 was added gene: ARHGAP42 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARHGAP42 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARHGAP42 were set to 34232960 Phenotypes for gene: ARHGAP42 were set to Interstitial lung disease; systemic hypertension; immunological abnormalities Review for gene: ARHGAP42 was set to RED Added comment: Single individual reported with homozygous LoF variant, chILD disorder, systemic hypertension, and immunological findings. Sources: Literature |
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| Mendeliome v0.8344 | KIAA0556 | Zornitza Stark Tag new gene name tag was added to gene: KIAA0556. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8342 | KIAA0556 | Zornitza Stark Mode of inheritance for gene: KIAA0556 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8335 | LINGO4 |
Laura Raiti gene: LINGO4 was added gene: LINGO4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LINGO4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LINGO4 were set to PMID: 33098801 Phenotypes for gene: LINGO4 were set to Developmental Delay, Intellectual disability, speech disorder Review for gene: LINGO4 was set to GREEN Added comment: 3 unrelated individuals 1 x individual compound heterozygous for 2x missense variants: c.679C>A; c.1262G>A p.Leu227Met; p.Arg421Gln comp het. Phenotype: infancy-onset generalized dystonia; DD/hypo, ID, speech disorder (isolated plus non-MD symptoms) NDD 1 x individual homozygous for missense variant: c.679C>A p.Leu227Met Phenotype: DD/hypo, ID, speech disorder 1 x individual homozygous for missense variant: c.1673G>A p.Ser558Asn Phenotype: DD/hypo, ID, speech disorder Sources: Literature |
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| Mendeliome v0.8335 | ARFGEF3 |
Laura Raiti gene: ARFGEF3 was added gene: ARFGEF3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARFGEF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARFGEF3 were set to PMID: 33098801 Phenotypes for gene: ARFGEF3 were set to Dystonia Review for gene: ARFGEF3 was set to GREEN Added comment: 3 x unrelated individuals 1 x de novo missense variant: c.6212T>C p.Met2071Thr, phenotype: infancy-onset generalized dystonia (isolated) 1x stop-gain variant c.1773T>G p.Tyr591* (inherited from mosaic mother), phenotype: infancy-onset generalized dystonia (isolated) 1 x de novo missense variant (Gene Matcher) c.250A>C p.Met84Leu childhood-onset generalized dystonia (isolated) Sources: Literature |
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| Mendeliome v0.8335 | IMPDH2 |
Laura Raiti gene: IMPDH2 was added gene: IMPDH2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IMPDH2 were set to PMID: 33098801 Phenotypes for gene: IMPDH2 were set to Dystonia Review for gene: IMPDH2 was set to GREEN Added comment: 6 unrelated individuals 1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein. IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition. 1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified: 3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg) 1 x deletion: c.478_480delTCC (p.Ser160del) The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair. The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1. The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2. Sources: Literature |
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| Mendeliome v0.8333 | KIF20A |
Zornitza Stark gene: KIF20A was added gene: KIF20A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF20A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF20A were set to 29357359 Phenotypes for gene: KIF20A were set to Cardiomyopathy, familial restrictive, 6, MIM# 619433 Review for gene: KIF20A was set to GREEN Added comment: Single family reported, two affected sibs, perinatal lethal cardiomyopathy, compound het variants in this gene. Sources: Literature |
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| Mendeliome v0.8329 | B2M | Zornitza Stark Mode of inheritance for gene: B2M was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8324 | TMEM126A | Zornitza Stark Mode of inheritance for gene: TMEM126A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8322 | MYC | Zornitza Stark Mode of inheritance for gene: MYC was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8317 | ATG7 |
Zornitza Stark gene: ATG7 was added gene: ATG7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATG7 were set to 34161705 Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422 Review for gene: ATG7 was set to GREEN Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk. Sources: Literature |
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| Mendeliome v0.8314 | ADA | Zornitza Stark Mode of inheritance for gene: ADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8312 | C2orf69 |
Zornitza Stark gene: C2orf69 was added gene: C2orf69 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C2orf69 were set to 34038740; 33945503 Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423 Review for gene: C2orf69 was set to GREEN Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model. PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures. Sources: Literature |
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| Mendeliome v0.8306 | NYNRIN |
Laura Raiti gene: NYNRIN was added gene: NYNRIN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NYNRIN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NYNRIN were set to PMID: 30885698 Review for gene: NYNRIN was set to AMBER Added comment: 3 individuals with Wilms Tumour reported (2 children from 1 family, the 3rd child from a second family). Biallelic truncating mutations in NYNRIN in three children with Wilms Tumour from two families, each parent was heterozygous for one of the mutations. One of the affected children had an inguinal hernia and another had epilepsy, hypothyroidism, and intellectual disability. Sources: Literature |
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| Mendeliome v0.8303 | ZC3H14 | Zornitza Stark Mode of inheritance for gene: ZC3H14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8300 | IRX5 | Zornitza Stark Tag SV/CNV tag was added to gene: IRX5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8298 | IRX5 | Zornitza Stark Mode of inheritance for gene: IRX5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8293 | CXCR2 |
Zornitza Stark gene: CXCR2 was added gene: CXCR2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CXCR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CXCR2 were set to 24777453 Phenotypes for gene: CXCR2 were set to WHIM syndrome 2, 619407 Review for gene: CXCR2 was set to RED Added comment: 2 sisters with neutropaenia, myelokathexis, and recurrent bacterial infections and homozygous frameshift variant in this gene. Sources: Expert list |
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| Mendeliome v0.8292 | RING1 |
Eleanor Williams gene: RING1 was added gene: RING1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RING1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RING1 were set to 29386386 Phenotypes for gene: RING1 were set to microcephaly; intellectual disability Review for gene: RING1 was set to RED Added comment: Not associated with any phenotype in OMIM. PMID: 29386386 - Pierce et al 2018 - report a 13 yo female with a de novo RING1 p.R95Q variant and syndromic neurodevelopmental disabilities. Early motor and language development were normal but were delayed after the first year of life. Cognitive testing showed a verbal IQ of 55 and a visual performance IQ of 63. Head circumference at birth was -4.9 SD, and -4.2 SD at age 13 which falls into the severe microcephaly category. C. elegans with either the missense mutation or complete knockout of spat-3 (the suggested RING1 ortholog) were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance. Sources: Literature |
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| Mendeliome v0.8292 | RNF2 |
Eleanor Williams gene: RNF2 was added gene: RNF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RNF2 were set to 33864376 Phenotypes for gene: RNF2 were set to epilepsy; intellectual disability; intrauterine growth retardation Review for gene: RNF2 was set to AMBER Added comment: Not associated with any phenotype in OMIM. PMID:33864376 (Luo et al 2021) report 2 cases of children with de novo missense variants (p.R70H and p.S82R) in RNF2 and a phenotype of intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Seizures started in infancy. Both variants are absent from gnomad. Functional studies in Drosophila showed that the disease-linked variants (p.R70H and p.S82R) behave as LoF alleles. Sources: Literature |
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| Mendeliome v0.8292 | IRX5 |
Eleanor Williams changed review comment from: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition. Cone dystrophy ------------------- PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments. Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected. They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.; to: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition (PMID: 22581230;17230486) Duplication of gene ------------------- PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments. Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected. They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae. Loss of function/gene --------- PMID: 28041643 - Carss et al 2017 - screened a cohort of 722 individuals with inherited retinal disease using WES/WGS. 1 case reported with a biallelic deletion in IRX5 reported which leads to a frameshift ENST00000394636.4; c.1362_1366delTAAAG, p.Lys455ProfsTer19 in a patient with retinitis pigmentosa. PMID: 32045705 - Apuzzo et al 2020 - report 2 cases of loss of a region in 16q12.1q21 which encompasses IRX5 and IRX6 and many other genes, which together with 3 other previous reports of deletions in this region help define a syndrome with features that include dysmorphic features, short stature, microcephaly, global developmental delay/intellectual disability, autism spectrum disorder (ASD) and ocular abnormalities (nystagmus and strabismus). |
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| Mendeliome v0.8292 | IRX6 |
Eleanor Williams changed review comment from: Not associated with any disorder in OMIM or Gene2Phenotype. PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments. Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected. They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae. Sources: Literature; to: Not associated with any disorder in OMIM or Gene2Phenotype. PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments. Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected. They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae. Sources: Literature |
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| Mendeliome v0.8289 | HID1 |
Zornitza Stark gene: HID1 was added gene: HID1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HID1 were set to 33999436 Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism Review for gene: HID1 was set to GREEN Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy Sources: Literature |
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| Mendeliome v0.8286 | KIF1B | Zornitza Stark Mode of inheritance for gene: KIF1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8281 | FYCO1 | Zornitza Stark Mode of inheritance for gene: FYCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8274 | MYT1 | Zornitza Stark Mode of inheritance for gene: MYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8270 | ATP1A2 | Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8264 | IRX6 |
Eleanor Williams gene: IRX6 was added gene: IRX6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IRX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: IRX6 were set to 33891002 Phenotypes for gene: IRX6 were set to cone dystrophy, MONDO:0000455 Mode of pathogenicity for gene: IRX6 was set to Other Review for gene: IRX6 was set to GREEN Added comment: Not associated with any disorder in OMIM or Gene2Phenotype. PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments. Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected. They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae. Sources: Literature |
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| Mendeliome v0.8264 | EPHA7 | Zornitza Stark Tag SV/CNV tag was added to gene: EPHA7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8263 | EPHA7 |
Zornitza Stark gene: EPHA7 was added gene: EPHA7 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: EPHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EPHA7 were set to 34176129 Phenotypes for gene: EPHA7 were set to Intellectual disability Review for gene: EPHA7 was set to AMBER Added comment: Lévy et al (2021 - PMID: 34176129) provide evidence that haploinssuficiency of EPHA7 results in a neurodevelopmental disorder. The authors report on 12 individuals belonging to 9 unrelated families, all harboring with 6q microdeletions spanning EPHA7. Overlapping features included DD (13/13), ID (10/10 - mild in most cases, individuals with larger CNVs/additional variants had more severe phenotype), speech delay and behavioral disorders. Variable other features incl. hypotonia (70%), non specific facial features, eye abnormalities (40%) and cardiac defects (25%). The CNVs ranged from 152 kb to few Mb in size but in 4 subjects (P5-8) were only minimal, involving only EPHA7. 9 out of 12 individuals had inherited the deletion (5 subjects paternal, 4 maternal), in 1 subject (P12) this occured de novo, while for 2 others inheritance was not specified. Most deletions were inherited from an unaffected parent (in 6/7 families), with unclear contribution in a further one. The authors discuss on previous studies suggesting an important role for EphA7 in brain development (modulation of cell-cell adhesion and repulsion, regulation of dendrite morphogenesis in early corticogenesis, role in dendritic spine formation later in development. EphA7 has also been proposed to drive neuronal maturation and synaptic function). Haploinsufficiency for other ephrins or ephrin receptors has been implicated in other NDDs. Overall Lévy et al promote incomplete penetrance and variable expressivity with haploinsufficiency of this gene being a risk factor for NDD. [The gene has also an %HI of 2.76% and a pLI of 1]. Sources: Expert Review |
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| Mendeliome v0.8260 | DNM1 | Zornitza Stark Mode of inheritance for gene: DNM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8258 | GRK2 |
Zornitza Stark gene: GRK2 was added gene: GRK2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GRK2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GRK2 were set to 33200460 Phenotypes for gene: GRK2 were set to Jeune asphyxiating thoracic dystrophy (ATD) Review for gene: GRK2 was set to AMBER Added comment: Two unrelated families reported and some functional data. Sources: Literature |
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| Mendeliome v0.8255 | WDR60 | Zornitza Stark Mode of inheritance for gene: WDR60 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8252 | WDR34 | Zornitza Stark Mode of inheritance for gene: WDR34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8249 | WDR19 | Zornitza Stark Mode of inheritance for gene: WDR19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8246 | TXNDC15 | Zornitza Stark Mode of inheritance for gene: TXNDC15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8243 | TTC8 | Zornitza Stark Mode of inheritance for gene: TTC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8240 | TTC21B | Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8237 | TRAF3IP1 | Zornitza Stark Mode of inheritance for gene: TRAF3IP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8234 | OBSCN |
Zornitza Stark Tag refuted was removed from gene: OBSCN. Tag disputed tag was added to gene: OBSCN. |
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| Mendeliome v0.8233 | OBSCN | Zornitza Stark Tag refuted tag was added to gene: OBSCN. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8229 | ATP9A |
Arina Puzriakova gene: ATP9A was added gene: ATP9A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATP9A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP9A were set to http://dx.doi.org/10.1136/jmedgenet-2021-107843 Phenotypes for gene: ATP9A were set to Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms Review for gene: ATP9A was set to AMBER Added comment: Vogt et al. 2021 report on 3 individuals from 2 unrelated consanguineous families with different homozygous truncating variants in ATP9A, presenting with DD/ID of variable degree (2 mild, 1 severe), postnatal microcephaly (OFC range: −2.33 SD to −3.58 SD), failure to thrive, and gastrointestinal symptoms. Patient-derived fibroblasts showed reduced expression of ATP9A, and consistent with previous findings also overexpression of interacting partners, ARPC3 and SNX3. Sources: Literature |
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| Mendeliome v0.8229 | ATP2C2 |
Eleanor Williams gene: ATP2C2 was added gene: ATP2C2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATP2C2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATP2C2 were set to 33864365; 28440294 Phenotypes for gene: ATP2C2 were set to language impairment, HP:0002463 Review for gene: ATP2C2 was set to RED Added comment: PMID: 33864365 - Martinelli et al 2021 - report a family with a missense variant NM_001286527.2:c.304G>A, p.(Val102Met) in ATP2C2 in a father and two siblings with specific language impairment. However two other affected siblings did not have this variant. This variant was also reported by Chen et al. They found that the variant had a higher frequency in language cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). They postulate that variant is not sufficient on its own to cause a disorder but is a susceptibility factor which increases the risk for language impairment. PMID: 28440294 - Chen et al 2017 - report 2 probands with severe learning impairment, and missense variants in ATP2C2 (NM_001286527: c.G304A:p.V102M and NM_001291454:exon21: c.C1936T:p.R646W). Sources: Literature |
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| Mendeliome v0.8227 | TMEM67 | Zornitza Stark Mode of inheritance for gene: TMEM67 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8224 | XDH | Zornitza Stark Mode of inheritance for gene: XDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8221 | TCTEX1D2 | Zornitza Stark Mode of inheritance for gene: TCTEX1D2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8218 | TCTN3 | Zornitza Stark Mode of inheritance for gene: TCTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8215 | SDCCAG8 | Zornitza Stark Mode of inheritance for gene: SDCCAG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8213 | SBDS | Zornitza Stark Mode of inheritance for gene: SBDS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8210 | RPGRIP1L | Zornitza Stark Mode of inheritance for gene: RPGRIP1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8207 | NPHP4 | Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8204 | NPHP1 | Zornitza Stark Mode of inheritance for gene: NPHP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8203 | NPHP1 | Zornitza Stark Tag SV/CNV tag was added to gene: NPHP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8202 | TIE1 |
Zornitza Stark gene: TIE1 was added gene: TIE1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TIE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TIE1 were set to 32947856; 24764452 Phenotypes for gene: TIE1 were set to Lymphatic malformation 11, MIM# 619401 Review for gene: TIE1 was set to AMBER Added comment: Three families reported, supportive animal model, though variants are missense and present at a low frequency in gnomad. Sources: Literature |
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| Mendeliome v0.8201 | NUF2 |
Dean Phelan gene: NUF2 was added gene: NUF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NUF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NUF2 were set to PMID: 33721060 Phenotypes for gene: NUF2 were set to microcephaly; short stature; bilateral vocal cord paralysis; micrognathia; atrial septal defect Review for gene: NUF2 was set to RED Added comment: PMID: 33721060 - de novo missense variant identified in one male patient with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect. Sources: Literature |
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| Mendeliome v0.8201 | ERGIC3 |
Elena Savva gene: ERGIC3 was added gene: ERGIC3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ERGIC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERGIC3 were set to PMID: 33710394; 31585110 Phenotypes for gene: ERGIC3 were set to Intellectual disability Review for gene: ERGIC3 was set to AMBER Added comment: PMID: 33710394 - two homozygous sibs with mild ID, a novel canonical splice (c.717+1G>A). Absent in gnomAD, no splice studies. Classed as a VUS. PMID: 31585110 - 1 hom (p.Gln233Argfs*10) in a male 8yo with Growth retardation, Microcephaly, Learning disability, Facial dysmorphism, Abnormal pigmentation. Sources: Literature |
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| Mendeliome v0.8201 | HEATR5B |
Teresa Zhao gene: HEATR5B was added gene: HEATR5B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HEATR5B were set to PMID: 33824466 Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia Review for gene: HEATR5B was set to AMBER Added comment: Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay. Two homozygous splice variants were reported ((c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. Homozygous knockout mice were not viable. *NOTE: gene (and alias) not found in OMIM Sources: Literature |
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| Mendeliome v0.8199 | NEK8 | Zornitza Stark Mode of inheritance for gene: NEK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8196 | MKKS | Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8193 | IQCB1 | Zornitza Stark Mode of inheritance for gene: IQCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8190 | IFT80 | Zornitza Stark Mode of inheritance for gene: IFT80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8187 | LZTFL1 | Zornitza Stark Mode of inheritance for gene: LZTFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8185 | TTC26 |
Zornitza Stark gene: TTC26 was added gene: TTC26 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC26 were set to 34177428; 32617964; 31595528; 24596149; 22718903 Phenotypes for gene: TTC26 were set to Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations Review for gene: TTC26 was set to GREEN Added comment: Three unrelated families and functional data including zebrafish model. Sources: Literature |
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| Mendeliome v0.8181 | IFT43 | Zornitza Stark Mode of inheritance for gene: IFT43 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8178 | IFT140 | Zornitza Stark Mode of inheritance for gene: IFT140 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8177 | ARHGEF9 | Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8173 | DYNC2H1 | Zornitza Stark Mode of inheritance for gene: DYNC2H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8170 | DDX59 | Zornitza Stark Mode of inheritance for gene: DDX59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8167 | CEP83 | Zornitza Stark Mode of inheritance for gene: CEP83 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8165 | RNU12 |
Bryony Thompson gene: RNU12 was added gene: RNU12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU12 were set to 34085356; 27863452 Phenotypes for gene: RNU12 were set to CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations Review for gene: RNU12 was set to GREEN Added comment: 5 CDAGS syndrome families with biallelic variants all including NC_000022.10:g.43011402C>T and another variant on the second allele. Whole transcriptome sequencing analysis of patient lymphoblastoid cells identified differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events. Also, limited evidence for an association with cerebellar ataxia with a single large consanguineous family reported with a homozygous variant. Sources: Literature |
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| Mendeliome v0.8162 | FHOD3 | Zornitza Stark Mode of inheritance for gene: FHOD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8161 | FHOD3 | Zornitza Stark Tag SV/CNV tag was added to gene: FHOD3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8159 | KCNJ16 |
Zornitza Stark gene: KCNJ16 was added gene: KCNJ16 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KCNJ16 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KCNJ16 were set to 33811157; 33840812 Phenotypes for gene: KCNJ16 were set to Renal tubulopathy; deafness Review for gene: KCNJ16 was set to GREEN Added comment: 8 unrelated families reported. Sources: Literature |
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| Mendeliome v0.8156 | KLHL7 | Zornitza Stark Mode of inheritance for gene: KLHL7 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8153 | SLC34A3 | Zornitza Stark Mode of inheritance for gene: SLC34A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8150 | TNC | Zornitza Stark Mode of inheritance for gene: TNC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8146 | RIPK4 | Zornitza Stark Mode of inheritance for gene: RIPK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8143 | CEP290 | Zornitza Stark Mode of inheritance for gene: CEP290 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8140 | CEP164 | Zornitza Stark Mode of inheritance for gene: CEP164 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8137 | CEP120 | Zornitza Stark Mode of inheritance for gene: CEP120 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8134 | CEP104 | Zornitza Stark Mode of inheritance for gene: CEP104 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8133 | C5orf42 | Zornitza Stark Tag new gene name tag was added to gene: C5orf42. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8131 | C5orf42 | Zornitza Stark Mode of inheritance for gene: C5orf42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8130 | C21orf2 | Zornitza Stark Tag new gene name tag was added to gene: C21orf2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8128 | C21orf2 | Zornitza Stark Mode of inheritance for gene: C21orf2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8125 | BBS9 | Zornitza Stark Mode of inheritance for gene: BBS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8122 | BBS7 | Zornitza Stark Mode of inheritance for gene: BBS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8119 | BBS5 | Zornitza Stark Mode of inheritance for gene: BBS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8116 | BBS4 | Zornitza Stark Mode of inheritance for gene: BBS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8113 | ARL6 | Zornitza Stark Mode of inheritance for gene: ARL6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8109 | SLCO2A1 | Zornitza Stark Mode of inheritance for gene: SLCO2A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8104 | PPP2R1A | Zornitza Stark Mode of inheritance for gene: PPP2R1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8098 | CLPB | Zornitza Stark Mode of inheritance for gene: CLPB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8092 | ABCB4 | Zornitza Stark Mode of inheritance for gene: ABCB4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8089 | OAS1 | Zornitza Stark Mode of pathogenicity for gene: OAS1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8088 | OAS1 | Zornitza Stark Mode of inheritance for gene: OAS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8086 | SLIT3 |
Zornitza Stark gene: SLIT3 was added gene: SLIT3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLIT3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLIT3 were set to 33933663 Phenotypes for gene: SLIT3 were set to Congenital diaphragmatic hernia Review for gene: SLIT3 was set to AMBER Added comment: Two affected individuals, single family, supportive mouse model. Sources: Literature |
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| Mendeliome v0.8083 | IQGAP3 |
Zornitza Stark gene: IQGAP3 was added gene: IQGAP3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IQGAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: IQGAP3 were set to Hereditary neuropathy Review for gene: IQGAP3 was set to RED Added comment: Single multiplex family, intronic variant, limited functional data. Sources: Literature |
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| Mendeliome v0.8080 | TINF2 | Zornitza Stark Mode of inheritance for gene: TINF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8079 | POPDC3 |
Zornitza Stark changed review comment from: 5 affected individuals from 3 unrelated families reported, supportive animal model data. Sources: Literature; to: 5 affected individuals from 3 unrelated families reported, supportive animal model data. Presentation was between adolescence and 40s with proximal muscle weakness primarily affecting the lower limbs, resulting in increased falls and difficulty running. The disorder was slowly progressive, with later involvement of the upper limbs. MRI showed fatty replacement of the thigh muscles and medial gastrocnemius, with some paraspinal muscles also affected. Some patients had calf hypertrophy. Serum CK was markedly elevated. Sources: Literature |
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| Mendeliome v0.8078 | POPDC3 |
Zornitza Stark gene: POPDC3 was added gene: POPDC3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POPDC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POPDC3 were set to 31610034 Phenotypes for gene: POPDC3 were set to Muscular dystrophy, limb-girdle, autosomal recessive 26, MIM# 618848 Review for gene: POPDC3 was set to GREEN Added comment: 5 affected individuals from 3 unrelated families reported, supportive animal model data. Sources: Literature |
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| Mendeliome v0.8075 | ACD | Zornitza Stark Mode of inheritance for gene: ACD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8069 | WRAP53 | Zornitza Stark Mode of inheritance for gene: WRAP53 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8069 | WRAP53 | Zornitza Stark Mode of inheritance for gene: WRAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8066 | EP300 | Zornitza Stark Mode of inheritance for gene: EP300 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8063 | PARN | Zornitza Stark Mode of inheritance for gene: PARN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8060 | KLF1 | Zornitza Stark Mode of inheritance for gene: KLF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8059 | SPAG17 |
Zornitza Stark gene: SPAG17 was added gene: SPAG17 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPAG17 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPAG17 were set to 28548327 Phenotypes for gene: SPAG17 were set to Spermatogenic failure 55, MIM#619380 Review for gene: SPAG17 was set to RED Added comment: Single family reported with two affected brothers, homozygous missense variant. Sources: Literature |
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| Mendeliome v0.8058 | CATIP |
Zornitza Stark gene: CATIP was added gene: CATIP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CATIP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CATIP were set to 32503832 Phenotypes for gene: CATIP were set to Spermatogenic failure 54, MIM# 619379 Review for gene: CATIP was set to RED Added comment: Homozygous missense variant reported in a single consanguineous family with 4 affecteds. Limited functional data. Sources: Expert list |
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| Mendeliome v0.8054 | HAX1 | Zornitza Stark Mode of inheritance for gene: HAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8047 | ARCN1 | Zornitza Stark Mode of inheritance for gene: ARCN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8044 | NBEAL2 | Zornitza Stark Mode of inheritance for gene: NBEAL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8041 | GFI1 | Zornitza Stark Mode of inheritance for gene: GFI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8038 | SLC13A5 | Zornitza Stark Mode of inheritance for gene: SLC13A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8035 | GATA2 | Zornitza Stark Mode of inheritance for gene: GATA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8033 | GATA1 | Zornitza Stark Mode of inheritance for gene: GATA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8030 | ELANE | Zornitza Stark Mode of inheritance for gene: ELANE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8027 | EFL1 | Zornitza Stark Mode of inheritance for gene: EFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8024 | CXCR4 | Zornitza Stark Mode of inheritance for gene: CXCR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8021 | CTC1 | Zornitza Stark Mode of inheritance for gene: CTC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8018 | ANKRD26 | Zornitza Stark Mode of inheritance for gene: ANKRD26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8017 | ANKRD26 | Zornitza Stark Tag 5'UTR tag was added to gene: ANKRD26. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8015 | AK2 | Zornitza Stark Mode of inheritance for gene: AK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8012 | ADA2 | Zornitza Stark Mode of inheritance for gene: ADA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8008 | RFX4 |
Zornitza Stark gene: RFX4 was added gene: RFX4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RFX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RFX4 were set to 33658631 Phenotypes for gene: RFX4 were set to ID, ASD, ADHD Review for gene: RFX4 was set to GREEN Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis. Sources: Literature |
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| Mendeliome v0.8006 | RFX3 |
Zornitza Stark gene: RFX3 was added gene: RFX3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RFX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RFX3 were set to 33658631 Phenotypes for gene: RFX3 were set to ID, ASD, ADHD Review for gene: RFX3 was set to GREEN Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis. Sources: Literature |
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| Mendeliome v0.8004 | RFX7 |
Zornitza Stark gene: RFX7 was added gene: RFX7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RFX7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RFX7 were set to 33658631 Phenotypes for gene: RFX7 were set to ID, ASD, ADHD Review for gene: RFX7 was set to GREEN Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis. Sources: Literature |
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| Mendeliome v0.8002 | SEMA3F |
Zornitza Stark gene: SEMA3F was added gene: SEMA3F was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEMA3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEMA3F were set to 33495532 Phenotypes for gene: SEMA3F were set to Hypogonadotropic hypogonadism Review for gene: SEMA3F was set to GREEN Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 10 individuals from 7 families with heterozygous SEMA3F missense variants. In 4 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Provide unequivocal human embryonic data showing the expression of SEMA3F along the developing human GnRH migratory pathway. SEMA3Fs harboring the P452T, T29M, and T724M missense variants showed impaired SEMA3F secretion in whole cell lysates. Sources: Literature |
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| Mendeliome v0.8000 | PLXNA3 |
Zornitza Stark gene: PLXNA3 was added gene: PLXNA3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLXNA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PLXNA3 were set to 33495532 Phenotypes for gene: PLXNA3 were set to Hypogonadotropic hypogonadism Review for gene: PLXNA3 was set to GREEN Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 7 individuals from 5 families with hemizygous PLXNA3 missense variants. In 2 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Data provided with evidence that PLXNA3, a key component of the SEMA3F holoreceptor complex,31 is expressed by the human GnRH and olfactory/vomeronasal systems. S646P variant showed PLXNA3 localization exclusively in the ER, indicating that the variant S646P disrupts cell surface localization of PLXNA3. Sources: Literature |
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| Mendeliome v0.7995 | GNAI1 | Zornitza Stark Mode of inheritance for gene: GNAI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7993 | FARSA | Zornitza Stark edited their review of gene: FARSA: Added comment: Schuch et al. (2021) report 3 unrelated individuals with bi-allelic variants in FARSA. Identified through WES and variants segregated with disease. Functional evidence was obtained with reduced FARS1 enzyme activity levels in fibroblasts or EBV-transformed lymphoblastoid cell lines (EBV-LCLs) of patients. Common to all was a chronic interstitial lung disease starting early in life and characterized by bilateral ground-glass opacification on HR-CT, and cholesterol pneumonitis in lung histology. Additional abnormalities in other organ systems include liver disease, neurological manifestations, and growth restriction.; Changed rating: GREEN; Changed publications: 31355908, 33598926; Changed phenotypes: Rajab interstitial lung disease with brain calcifications 2, MIM# 619013 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7991 | LAMA5 | Bryony Thompson Mode of inheritance for gene: LAMA5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7988 | ZNF81 | Zornitza Stark Mode of inheritance for gene: ZNF81 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7986 | RELN |
Ee Ming Wong edited their review of gene: RELN: Added comment: - Six affected individuals carrying missense variants in RELN including 1. Two individuals with compound heterozygous variants - One of the variants has 26 homozygotes in gnomAD and therefore pathogenicity of this variant is in question - LoF demonstrated for three of the variants (reduced RELN secretion), except for p.Y1821H which demonstrated an apparently increased RELN secretion (GoF) 2. Two brothers carrying the maternally inherited variant (mother apparently healthy) - LoF demonstrated for these variants 3. Two individuals de novo for RELN variants - Dominant negative demonstrated for these variants where secretion of WT-RELN was impaired when co-transfected with mutant constructs in HEK293T cells; Changed rating: AMBER; Changed publications: Riva et al bioRxiv (pre-print, not peer-reviewed); Changed phenotypes: Pachygyria, Polymicrogyria, Heterotopia; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.7985 | NIID |
Bryony Thompson STR: NIID was added STR: NIID was added to Mendeliome. Sources: Literature Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102 Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Tremor, hereditary essential, 6 MIM#618866 Review for STR: NIID was set to GREEN STR: NIID was marked as clinically relevant Added comment: NM_001364012.2:c.-164GGC[(66_517)] Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease. Normal repeat range: 7-60 Pathogenic repeat range: >=61-500 Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals. Sources: Literature |
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| Mendeliome v0.7982 | TRPM6 | Zornitza Stark Mode of inheritance for gene: TRPM6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7979 | CNTNAP1 | Zornitza Stark Mode of inheritance for gene: CNTNAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7976 | GLDN | Zornitza Stark Mode of inheritance for gene: GLDN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7974 | ZBTB42 |
Zornitza Stark gene: ZBTB42 was added gene: ZBTB42 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ZBTB42 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZBTB42 were set to 25055871 Phenotypes for gene: ZBTB42 were set to Lethal congenital contracture syndrome 6, MIM# 616248 Review for gene: ZBTB42 was set to AMBER Added comment: Homozygous missense variant reported in a family with three stillbirths and a phenotype consistent with LCCS. Supportive zebrafish model. Sources: Expert Review |
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| Mendeliome v0.7971 | MYBPC1 | Zornitza Stark Mode of inheritance for gene: MYBPC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7965 | MUSK | Zornitza Stark Mode of inheritance for gene: MUSK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7962 | DOK7 | Zornitza Stark Mode of inheritance for gene: DOK7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7959 | TPM2 | Zornitza Stark Mode of inheritance for gene: TPM2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7956 | CHRNG | Zornitza Stark Mode of inheritance for gene: CHRNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7953 | CD207 | Zornitza Stark Mode of inheritance for gene: CD207 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7951 | KIF17 |
Zornitza Stark gene: KIF17 was added gene: KIF17 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF17 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF17 were set to 33922911; 30458707; 28341548 Phenotypes for gene: KIF17 were set to Microphthalmia; Coloboma Review for gene: KIF17 was set to RED Added comment: Two siblings reported with MAC spectrum and homozygous missense variant in this gene. Some pre-existing data linking KIF17 to eye development. Sources: Literature |
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| Mendeliome v0.7949 | SASH3 |
Zornitza Stark gene: SASH3 was added gene: SASH3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SASH3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SASH3 were set to 33876203 Phenotypes for gene: SASH3 were set to Combined immunodeficiency; immune dysregulation Review for gene: SASH3 was set to GREEN Added comment: Four unrelated males reported presenting with combined immunodeficiency and immune dysregulation manifesting as recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopaenias. One missense variant, rest were nonsense. Sources: Literature |
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| Mendeliome v0.7947 | FOXP1 | Zornitza Stark Mode of inheritance for gene: FOXP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7945 | MYBPC2 |
Zornitza Stark gene: MYBPC2 was added gene: MYBPC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYBPC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYBPC2 were set to 32732226 Phenotypes for gene: MYBPC2 were set to Fetal akinesia; Hydrops; Hygroma; Multiple pterygium Review for gene: MYBPC2 was set to RED Added comment: Novel candidate gene identified in a fetus with fetal akinesia detected by ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, hygroma, multiple pterygium. A homozygous variant (c.3394G>A/ p.Glu1132Lys) in MYBPC2 was found by exome sequencing with concordant segregation among one affected sib and two unaffected sibs. Sources: Literature |
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| Mendeliome v0.7944 | SCN7A |
Zornitza Stark gene: SCN7A was added gene: SCN7A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SCN7A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCN7A were set to 32732226 Phenotypes for gene: SCN7A were set to Holoprosencephaly Review for gene: SCN7A was set to RED Added comment: Novel candidate gene identified in a fetus with holoprosencephaly detected by ultrasound. Autopsy showed multiple congenital abnormalities including IUGR, microcephaly, bilateral, ablepharon, corpus callosum agenesis, myelomeningocele, tracheal atresia, absent nipples, unilateral simian crease, and hypoplastic phalanges. Compound heterozygous variants including a truncating variant were found by exome sequencing with concordant segregation. Sources: Literature |
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| Mendeliome v0.7943 | SPTBN5 |
Zornitza Stark gene: SPTBN5 was added gene: SPTBN5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPTBN5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPTBN5 were set to 32732226; 28007035 Phenotypes for gene: SPTBN5 were set to Sacral agenesis; congenital anomalies Review for gene: SPTBN5 was set to RED Added comment: Identified as a candidate gene in a sacral agenesis cohort. PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis. Sources: Literature |
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| Mendeliome v0.7940 | WDR91 | Zornitza Stark Mode of inheritance for gene: WDR91 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7938 | WDR91 | Zornitza Stark commented on gene: WDR91: PMID 32732226: Novel candidate gene identified in a fetus with hygroma and hydrocephaly detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma, macrocephaly, abnormal ears, unilateral simian crease, hydrocephaly, cerebellar hypoplasia, and interventricular communication. A homozygous truncating variant was found by exome sequencing with concordant segregation among 4 affected fetus, 2 healthy sibs and both parents. Mouse models support role in brain development. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7938 | PLEKHN1 |
Zornitza Stark gene: PLEKHN1 was added gene: PLEKHN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLEKHN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLEKHN1 were set to 33884296 Phenotypes for gene: PLEKHN1 were set to Sensory Neuropathy Review for gene: PLEKHN1 was set to RED Added comment: Hom missense variant in single patient with severely reduced/absent pain and temperature sensation Sources: Literature |
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| Mendeliome v0.7937 | ZNF3 |
Zornitza Stark gene: ZNF3 was added gene: ZNF3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF3 were set to 32732226 Phenotypes for gene: ZNF3 were set to Hydrocephalus; cleft palate; microphthalmia Review for gene: ZNF3 was set to RED Added comment: Novel candidate gene identified in a fetus with hydrocephaly and facial cleft detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including a median cleft palate, partial maxillar agenesis, bilateral severe microphthalmia, arhinencephaly, partial thalamic fusion. A homozygous truncating variant (c.396A>G/ p.*132Trpext*69) in ZNF3 was found by exome sequencing. Sources: Literature |
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| Mendeliome v0.7936 | SMPDL3A |
Seb Lunke gene: SMPDL3A was added gene: SMPDL3A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SMPDL3A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMPDL3A were set to 33884296 Phenotypes for gene: SMPDL3A were set to Sensory Neuropathy Added comment: Hom missense variant in twin sisters with deverely reduced pain and temperature sensation Sources: Literature |
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| Mendeliome v0.7935 | WRAP73 |
Zornitza Stark gene: WRAP73 was added gene: WRAP73 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WRAP73 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WRAP73 were set to 33693649 Phenotypes for gene: WRAP73 were set to Microsperophakia Review for gene: WRAP73 was set to AMBER Added comment: Two Indian families with same homozygous missense, (p.Pro383Leu) and supportive functional data (zebrafish model). Sources: Literature |
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| Mendeliome v0.7930 | SLC37A4 | Zornitza Stark Mode of inheritance for gene: SLC37A4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7927 | TUBA1A | Zornitza Stark Mode of inheritance for gene: TUBA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7922 | BCAS3 | Zornitza Stark Mode of inheritance for gene: BCAS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7918 | SRCAP | Zornitza Stark Mode of inheritance for gene: SRCAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7915 | ADAMTSL2 | Zornitza Stark Mode of inheritance for gene: ADAMTSL2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7912 | HS3ST6 |
Zornitza Stark gene: HS3ST6 was added gene: HS3ST6 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HS3ST6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HS3ST6 were set to 33508266 Phenotypes for gene: HS3ST6 were set to Hereditary angioedema-8 (HAE8), MIM#619367 Review for gene: HS3ST6 was set to RED Added comment: Three affected individuals from a single family reported, missense variant, no functional data. Sources: Expert list |
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| Mendeliome v0.7911 | MYOF |
Zornitza Stark gene: MYOF was added gene: MYOF was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MYOF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MYOF were set to 32542751 Phenotypes for gene: MYOF were set to Hereditary angioedema-7 (HAE7), MIM#619366 Review for gene: MYOF was set to RED Added comment: Three individuals from one family reported, onset of recurrent episodic swelling of the face, lips, and oral mucosa was in the second decade. Variant was also present in another unaffected family member. Some functional data. Sources: Expert list |
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| Mendeliome v0.7908 | KNG1 | Zornitza Stark Mode of inheritance for gene: KNG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7903 | PLG | Zornitza Stark Mode of inheritance for gene: PLG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7899 | PRKD1 | Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7897 | PRKD1 |
Zornitza Stark edited their review of gene: PRKD1: Added comment: Additional publications supporting association with bi-allelic disease: PMID: 33919081: Three sisters with pulmonary stenosis, truncus arteriosis, and atrial septal defect were homozygous for c.265-1G>T. Their asymptomatic father was also homozygous, however he had two affected sisters (not genotyped), raising the possibility that PRKD1 may undergo autosomal recessive inheritance mode with gender limitation. PMID: 25713110: Two sisters with truncus arteriosis were homozygous for R618X.; Changed publications: 27479907, 32817298, 25713110, 33919081; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.7896 | ATXN2L |
Seb Lunke gene: ATXN2L was added gene: ATXN2L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATXN2L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATXN2L were set to 33283965; 33057194 Phenotypes for gene: ATXN2L were set to macrocephaly; intellectual disability Review for gene: ATXN2L was set to AMBER Added comment: Sources: Literature |
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| Mendeliome v0.7891 | LTBP1 |
Chern Lim gene: LTBP1 was added gene: LTBP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LTBP1 were set to 33991472 Phenotypes for gene: LTBP1 were set to cutis laxa syndrome Review for gene: LTBP1 was set to GREEN gene: LTBP1 was marked as current diagnostic Added comment: PMID:33991472 - Premature truncating variants in multiple affected individuals from 4 unrelated consanguineous families. - Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly). - Functional studies done on patient fibroblasts and zebrafish models. Sources: Literature |
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| Mendeliome v0.7891 | SLC30A5 |
Melanie Marty gene: SLC30A5 was added gene: SLC30A5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC30A5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC30A5 were set to 33547425; 12095919 Phenotypes for gene: SLC30A5 were set to Perinatal lethal cardiomyopathy Review for gene: SLC30A5 was set to AMBER Added comment: Four affected children from two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. 2 different homozygous PTCs variants found. Knockout of SLC30A5 in mouse models showed reduced body growth and reduced bone density. About 60% of the mice died due to bradyarrhythmia. Sources: Literature |
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| Mendeliome v0.7891 | CADM3 |
Teresa Zhao gene: CADM3 was added gene: CADM3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CADM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CADM3 were set to PMID: 33889941 Phenotypes for gene: CADM3 were set to Charcot-Marie-Tooth disease Review for gene: CADM3 was set to AMBER Added comment: Three families reported with the same missense variant in CADM3 p.Tyr172Cys (one family de novo), with mice work to show reduced expression of the mutant protein in axons and abnormal axonal organization. Sources: Literature |
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| Mendeliome v0.7891 | ANGPTL8 |
Dean Phelan gene: ANGPTL8 was added gene: ANGPTL8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ANGPTL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ANGPTL8 were set to PMID: 33909604 Phenotypes for gene: ANGPTL8 were set to Low serum triglycerides; Coronary artery disease Review for gene: ANGPTL8 was set to RED Added comment: PMID: 33909604 - Population studies showed PTV are associated with both lipid levels and coronary artery disease. Sources: Literature |
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| Mendeliome v0.7891 | PGM2L1 |
Chern Lim gene: PGM2L1 was added gene: PGM2L1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PGM2L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PGM2L1 were set to 33979636 Phenotypes for gene: PGM2L1 were set to severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris Review for gene: PGM2L1 was set to GREEN gene: PGM2L1 was marked as current diagnostic Added comment: PMID: 33979636: - Hom/chet PTVs in 4 unrelated individuals. All four affected individuals had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals. - Studies on patient fibroblasts and cell lines indicated that PGM2L1 deficiency causes a decrease, but not a disappearance, of the sugar bisphosphates needed for the formation of NDP-sugars and that there is no evidence that this leads to a glycosylation defect. Sources: Literature |
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| Mendeliome v0.7889 | KCNB1 | Zornitza Stark Mode of inheritance for gene: KCNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7886 | SYT1 | Zornitza Stark Mode of inheritance for gene: SYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7883 | UBTF | Zornitza Stark Mode of inheritance for gene: UBTF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7881 | ZEB2 | Zornitza Stark Tag SV/CNV tag was added to gene: ZEB2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7879 | SLC9A6 | Zornitza Stark Mode of inheritance for gene: SLC9A6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7876 | SHANK3 | Zornitza Stark Tag SV/CNV tag was added to gene: SHANK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7873 | SATB2 | Zornitza Stark Mode of inheritance for gene: SATB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7872 | MEF2C |
Zornitza Stark Tag SV/CNV tag was added to gene: MEF2C. Tag 5'UTR tag was added to gene: MEF2C. |
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| Mendeliome v0.7870 | MBD5 | Zornitza Stark Tag SV/CNV tag was added to gene: MBD5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7868 | MBD5 | Zornitza Stark Mode of inheritance for gene: MBD5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7861 | MASP1 | Zornitza Stark Mode of inheritance for gene: MASP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7858 | BRPF1 | Zornitza Stark Mode of inheritance for gene: BRPF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7855 | TRAF7 | Zornitza Stark Mode of inheritance for gene: TRAF7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7852 | UBE3B | Zornitza Stark Mode of inheritance for gene: UBE3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7843 | TAF6 | Zornitza Stark Mode of inheritance for gene: TAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7839 | SLC24A5 | Zornitza Stark Mode of inheritance for gene: SLC24A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7836 | SLC45A2 | Zornitza Stark Mode of inheritance for gene: SLC45A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7834 | TYR | Zornitza Stark Mode of inheritance for gene: TYR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7831 | TYRP1 | Zornitza Stark Mode of inheritance for gene: TYRP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7828 | MC1R | Zornitza Stark Mode of inheritance for gene: MC1R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7824 | LRMDA | Zornitza Stark Mode of inheritance for gene: LRMDA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7821 | SERPINF2 | Zornitza Stark Mode of inheritance for gene: SERPINF2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7818 | SERPINE1 | Zornitza Stark Mode of inheritance for gene: SERPINE1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7815 | TBXA2R | Zornitza Stark Mode of inheritance for gene: TBXA2R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7811 | P2RY12 | Zornitza Stark Mode of inheritance for gene: P2RY12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7808 | MCFD2 | Zornitza Stark Mode of inheritance for gene: MCFD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7805 | LMAN1 | Zornitza Stark Mode of inheritance for gene: LMAN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7802 | ITGA2B | Zornitza Stark Mode of inheritance for gene: ITGA2B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7799 | LMOD1 | Zornitza Stark Mode of inheritance for gene: LMOD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7796 | POU4F1 |
Bryony Thompson gene: POU4F1 was added gene: POU4F1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POU4F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU4F1 were set to 33783914; 8876243 Phenotypes for gene: POU4F1 were set to Ataxia; intention tremor; hypotonia Review for gene: POU4F1 was set to GREEN Added comment: 4 unrelated probands presenting with paediatric onset ataxia, intention tremor, and hypotonia, with de novo loss of function variants, and supporting null mouse model. Sources: Literature |
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| Mendeliome v0.7793 | HPS6 | Zornitza Stark Mode of inheritance for gene: HPS6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7790 | HPS4 | Zornitza Stark Mode of inheritance for gene: HPS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7787 | HPS3 | Zornitza Stark Mode of inheritance for gene: HPS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7784 | HPS1 | Zornitza Stark Mode of inheritance for gene: HPS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7781 | GP9 | Zornitza Stark Mode of inheritance for gene: GP9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7778 | GP6 | Zornitza Stark Mode of inheritance for gene: GP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7775 | GP1BB | Zornitza Stark Mode of inheritance for gene: GP1BB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7771 | SCNN1B | Zornitza Stark Mode of inheritance for gene: SCNN1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7768 | FGB | Zornitza Stark Mode of inheritance for gene: FGB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7765 | F9 | Zornitza Stark Mode of inheritance for gene: F9 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7762 | F8 | Zornitza Stark Mode of inheritance for gene: F8 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7759 | F7 | Zornitza Stark Mode of inheritance for gene: F7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7757 | F5 | Zornitza Stark Mode of inheritance for gene: F5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7754 | F13A1 | Zornitza Stark Mode of inheritance for gene: F13A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7751 | F10 | Zornitza Stark Mode of inheritance for gene: F10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7749 | MCM7 |
Arina Puzriakova gene: MCM7 was added gene: MCM7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM7 were set to 33654309; 34059554 Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency Review for gene: MCM7 was set to AMBER Added comment: MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present. ------ Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families. - PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment. Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression. - PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7. Sources: Literature |
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| Mendeliome v0.7747 | DTNBP1 | Zornitza Stark Mode of inheritance for gene: DTNBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7744 | BLOC1S3 | Zornitza Stark Mode of inheritance for gene: BLOC1S3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7741 | AP3B1 | Zornitza Stark Mode of inheritance for gene: AP3B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7738 | LHCGR | Zornitza Stark Mode of inheritance for gene: LHCGR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7734 | GEMIN5 |
Zornitza Stark gene: GEMIN5 was added gene: GEMIN5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GEMIN5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GEMIN5 were set to 33963192 Phenotypes for gene: GEMIN5 were set to Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, MIM# 619333 Review for gene: GEMIN5 was set to GREEN Added comment: Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy. 30 individuals from 22 unrelated families reported. Sources: Literature |
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| Mendeliome v0.7731 | ANO6 | Zornitza Stark Mode of inheritance for gene: ANO6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7728 | KLHL3 | Zornitza Stark Mode of inheritance for gene: KLHL3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7726 | KCNJ5 |
Zornitza Stark gene: KCNJ5 was added gene: KCNJ5 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KCNJ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNJ5 were set to 21311022; 22203740; 24420545; 24574546 Phenotypes for gene: KCNJ5 were set to Hyperaldosteronism, familial, type III, MIM# 613677 Review for gene: KCNJ5 was set to GREEN Added comment: Association with hyperaldosteronism: At least 5 unrelated families reported. Association with Long QT: disputed. Sources: Expert Review |
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| Mendeliome v0.7723 | HSD11B2 | Zornitza Stark Mode of inheritance for gene: HSD11B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7720 | CLCN2 | Zornitza Stark Mode of inheritance for gene: CLCN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7717 | CACNA1D | Zornitza Stark Mode of inheritance for gene: CACNA1D was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7714 | CACNA1H | Zornitza Stark Mode of inheritance for gene: CACNA1H was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7707 | NFU1 | Zornitza Stark Mode of inheritance for gene: NFU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7704 | RAB11B | Zornitza Stark Mode of inheritance for gene: RAB11B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7701 | UFSP2 | Zornitza Stark Mode of inheritance for gene: UFSP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7700 | KLHL13 |
Zornitza Stark gene: KLHL13 was added gene: KLHL13 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KLHL13 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: KLHL13 were set to 24627108 Phenotypes for gene: KLHL13 were set to HMSN Review for gene: KLHL13 was set to RED Added comment: Single family (two affected males) with an inherited peripheral neuropathy, no functional analysis. Sources: Expert Review |
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| Mendeliome v0.7697 | PRX | Zornitza Stark Mode of inheritance for gene: PRX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7694 | PLEKHG5 | Zornitza Stark Mode of inheritance for gene: PLEKHG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7691 | NEFL | Zornitza Stark Mode of inheritance for gene: NEFL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7688 | ADNP | Zornitza Stark Mode of inheritance for gene: ADNP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7685 | CHUK | Zornitza Stark Mode of inheritance for gene: CHUK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7682 | PARP6 | Zornitza Stark Mode of inheritance for gene: PARP6 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7680 | PARP6 |
Zornitza Stark gene: PARP6 was added gene: PARP6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PARP6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289 Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly Review for gene: PARP6 was set to GREEN Added comment: Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease. Sources: Literature |
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| Mendeliome v0.7677 | MAPKBP1 | Zornitza Stark Mode of inheritance for gene: MAPKBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7673 | DNAJB2 | Zornitza Stark Mode of inheritance for gene: DNAJB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7668 | TRPV6 | Zornitza Stark Mode of inheritance for gene: TRPV6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7662 | RETREG1 | Zornitza Stark Mode of inheritance for gene: RETREG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7659 | SBF1 | Zornitza Stark Mode of inheritance for gene: SBF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7656 | SBF2 | Zornitza Stark Mode of inheritance for gene: SBF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7653 | SCN10A | Zornitza Stark Mode of inheritance for gene: SCN10A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7649 | COL5A1 | Zornitza Stark Mode of inheritance for gene: COL5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7644 | DKC1 | Zornitza Stark Mode of inheritance for gene: DKC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7641 | THOC2 | Zornitza Stark Mode of inheritance for gene: THOC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7638 | FGA | Zornitza Stark Mode of inheritance for gene: FGA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7635 | GRHL2 | Zornitza Stark Mode of inheritance for gene: GRHL2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7632 | ST14 | Zornitza Stark Mode of inheritance for gene: ST14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7630 | CPE |
Zornitza Stark gene: CPE was added gene: CPE was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPE were set to 26120850; 32936766 Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326 Review for gene: CPE was set to AMBER Added comment: Four affected individuals from two unrelated families reported, bi-allelic LoF variants. Sources: Expert Review |
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| Mendeliome v0.7628 | CELSR1 |
Zornitza Stark gene: CELSR1 was added gene: CELSR1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770 Phenotypes for gene: CELSR1 were set to Lymphatic malformation 9, MIM# 619319 Review for gene: CELSR1 was set to GREEN Added comment: 3 unrelated families reported. Sources: Literature |
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| Mendeliome v0.7621 | SMARCA5 |
Zornitza Stark gene: SMARCA5 was added gene: SMARCA5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SMARCA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCA5 were set to 33980485 Phenotypes for gene: SMARCA5 were set to Neurodevelopmental disorder; microcephaly; dysmorphic features Review for gene: SMARCA5 was set to GREEN Added comment: 12 individuals reported with either de novo or appropriately segregating variants in this gene and mild developmental delay, frequent postnatal short stature and microcephaly, and recurrent dysmorphic features. Functional data supports gene-disease association. Sources: Literature |
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| Mendeliome v0.7616 | SEPT9 | Zornitza Stark Mode of inheritance for gene: SEPT9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7615 | SEPT9 |
Zornitza Stark Tag SV/CNV tag was added to gene: SEPT9. Tag 5'UTR tag was added to gene: SEPT9. Tag founder tag was added to gene: SEPT9. Tag new gene name tag was added to gene: SEPT9. |
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| Mendeliome v0.7613 | SLC5A7 | Zornitza Stark Mode of inheritance for gene: SLC5A7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7609 | NR3C2 | Zornitza Stark Mode of inheritance for gene: NR3C2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7606 | SCNN1A | Zornitza Stark Mode of inheritance for gene: SCNN1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7603 | SPTLC1 | Zornitza Stark Mode of inheritance for gene: SPTLC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7600 | SPTLC2 | Zornitza Stark Mode of inheritance for gene: SPTLC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7599 | ZPR1 | Zornitza Stark Tag founder tag was added to gene: ZPR1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7599 | ZPR1 |
Zornitza Stark gene: ZPR1 was added gene: ZPR1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZPR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZPR1 were set to 29851065 Phenotypes for gene: ZPR1 were set to Growth restriction, hypoplastic kidneys, alpecia, and distinctive facies 619321 Review for gene: ZPR1 was set to RED Added comment: 3 families reported with growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (GKAF). All were Hispanic families from the middle Rio Grande Valley. Homozygous missense identified in one family, p. Ile196Thr. Others unavailable for testing, founder effect postulated. Sources: Literature |
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| Mendeliome v0.7594 | AFF3 | Zornitza Stark Mode of inheritance for gene: AFF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7591 | KDR | Zornitza Stark Mode of inheritance for gene: KDR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7588 | TRIM2 | Zornitza Stark Mode of inheritance for gene: TRIM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7585 | RAB7A | Zornitza Stark Mode of inheritance for gene: RAB7A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7582 | PRDM12 | Zornitza Stark Mode of inheritance for gene: PRDM12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7573 | INTU | Zornitza Stark Mode of inheritance for gene: INTU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7570 | NGF | Zornitza Stark Mode of inheritance for gene: NGF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7565 | NDUFB3 | Zornitza Stark Mode of inheritance for gene: NDUFB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7557 | SPI1 |
Zornitza Stark gene: SPI1 was added gene: SPI1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPI1 were set to 33951726 Phenotypes for gene: SPI1 were set to Agammaglobulinaemia Review for gene: SPI1 was set to GREEN Added comment: Six unrelated individuals reported, four with de novo variants, two unphased. Some functional data. Sources: Literature |
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| Mendeliome v0.7554 | NDRG1 | Zornitza Stark Mode of inheritance for gene: NDRG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7551 | MTMR2 | Zornitza Stark Mode of inheritance for gene: MTMR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7549 | TMEM222 |
Zornitza Stark gene: TMEM222 was added gene: TMEM222 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM222 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM222 were set to 33824500 Phenotypes for gene: TMEM222 were set to Intellectual disability; Epilepsy; Microcephaly Review for gene: TMEM222 was set to GREEN Added comment: Polla et al (2021 - PMID: 33824500) report 17 individuals from 9 unrelated families, with biallelic TMEM222 pathogenic variants. The phenotype included motor, speech delay and moderate to severe ID (as universal features). Other manifestations included hypotonia (10/15), broad gait (5/12), seizures (7/17 - belonging to 6/9 families), MRI abnormalities (5/8). Variable behavioral abnormalities were observed (aggressive behavior, shy character, stereotypic movements etc). Abnormal OFC was a feature in several with microcephaly in 7 subjects from 4 families (measurements not available for all 17). Nonspecific facial features were reported in 10/17. Sources: Literature |
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| Mendeliome v0.7547 | CHD5 |
Zornitza Stark gene: CHD5 was added gene: CHD5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CHD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHD5 were set to 33944996 Phenotypes for gene: CHD5 were set to Intellectual disability; Epilepsy Review for gene: CHD5 was set to GREEN Added comment: 16 unrelated individuals reported with language deficits (81%), behavioral symptoms (69%), intellectual disability (64%), epilepsy (62%), and motor delay (56%). Sources: Literature |
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| Mendeliome v0.7544 | MME | Zornitza Stark Mode of inheritance for gene: MME was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7540 | RCAN1 |
Zornitza Stark gene: RCAN1 was added gene: RCAN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RCAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RCAN1 were set to 33863784 Phenotypes for gene: RCAN1 were set to FSGS; proteinuria Review for gene: RCAN1 was set to AMBER Added comment: Two families reported, some functional data. Sources: Literature |
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| Mendeliome v0.7537 | ZNFX1 |
Zornitza Stark gene: ZNFX1 was added gene: ZNFX1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNFX1 were set to 33872655; 33876776 Phenotypes for gene: ZNFX1 were set to Multisystem inflammation; susceptibility to viral infections Review for gene: ZNFX1 was set to GREEN Added comment: 15 individuals from 8 families reported with multi-system inflammation and susceptibility to viral infections. In addition, four indviduals from two unrelated kindreds reported with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis. Sources: Literature |
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| Mendeliome v0.7535 | STXBP3 |
Zornitza Stark gene: STXBP3 was added gene: STXBP3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: STXBP3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STXBP3 were set to 33891011 Phenotypes for gene: STXBP3 were set to Very Early Onset Inflammatory Bowel Disease; Bilateral Sensorineural Hearing Loss; Immune Dysregulation Review for gene: STXBP3 was set to GREEN Added comment: 10 individuals from 5 families reported. Sources: Literature |
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| Mendeliome v0.7532 | IL21R | Zornitza Stark Mode of inheritance for gene: IL21R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7529 | SIN3B | Zornitza Stark Mode of inheritance for gene: SIN3B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7519 | LRSAM1 | Zornitza Stark Mode of inheritance for gene: LRSAM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7516 | LITAF | Zornitza Stark Mode of inheritance for gene: LITAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7513 | SLC3A1 | Zornitza Stark Mode of inheritance for gene: SLC3A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7511 | LSM7 |
Bryony Thompson gene: LSM7 was added gene: LSM7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LSM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSM7 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100034 Phenotypes for gene: LSM7 were set to Leukodystrophy; foetal death Review for gene: LSM7 was set to AMBER Added comment: Homozygous variant (p.Asp41Asn) identified in a child with leukodystrophy and a homozygous variant (p.Arg69Pro) identified in an individual that died in utero. In vitro and in vivo (zebrafish) assays supporting pathogenicity of the 2 variants. Sources: Literature |
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| Mendeliome v0.7509 | PTPN4 |
Bryony Thompson gene: PTPN4 was added gene: PTPN4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTPN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PTPN4 were set to 17953619; 25424712; 30238967; DOI: https://doi.org/10.1016/j.xhgg.2021.100033 Phenotypes for gene: PTPN4 were set to Intellectual disability; developmental delay Review for gene: PTPN4 was set to GREEN Added comment: >3 unrelated probands and supporting mouse model PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines DOI: https://doi.org/10.1016/j.xhgg.2021.100033 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo. Sources: Literature |
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| Mendeliome v0.7507 | POLR3K | Zornitza Stark Tag founder tag was added to gene: POLR3K. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7506 | POLR3K |
Zornitza Stark gene: POLR3K was added gene: POLR3K was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3K were set to 30584594; 33659930 Phenotypes for gene: POLR3K were set to Hypomyelinating leukodystrophy-21, MIM#619310 Review for gene: POLR3K was set to AMBER Added comment: Two individuals from same ethnic background reported with a common homozygous missense variant in this gene, suggestive of founder effect. Some functional evidence, and note other gene family members are linked to similar phenotypes. Neurodegenerative phenotype: global developmental delay apparent from infancy with loss of motor, speech, and cognitive milestones in the first decades of life. Sources: Expert Review |
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| Mendeliome v0.7503 | SAG | Zornitza Stark Mode of inheritance for gene: SAG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7500 | YWHAG | Zornitza Stark Mode of inheritance for gene: YWHAG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7496 | OCRL | Zornitza Stark Mode of inheritance for gene: OCRL was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7489 | NEK1 | Zornitza Stark Mode of inheritance for gene: NEK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7486 | INF2 | Zornitza Stark Mode of inheritance for gene: INF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7483 | MED25 | Zornitza Stark Mode of inheritance for gene: MED25 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7480 | HSPB1 | Zornitza Stark Mode of inheritance for gene: HSPB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7477 | HINT1 | Zornitza Stark Mode of inheritance for gene: HINT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7474 | GNB4 | Zornitza Stark Mode of inheritance for gene: GNB4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7471 | GJB1 | Zornitza Stark Mode of inheritance for gene: GJB1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7470 | NEPRO |
Chern Lim gene: NEPRO was added gene: NEPRO was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NEPRO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEPRO were set to 26633546; 29620724; 31250547 Phenotypes for gene: NEPRO were set to Anauxetic dysplasia 3, MIM618853 Review for gene: NEPRO was set to AMBER Added comment: PMIDs 26633546, 29620724: 2 families with the same homozygous missense variant, haplotype analysis confirmed the founder nature of the variant. PMID 31250547: 1 family with homozygous novel missense All 5 affected individuals have severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. They also have short metacarpals, broad middle phalanges, and metaphyseal irregularities. No functional studies. Sources: Literature |
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| Mendeliome v0.7468 | FGD4 | Zornitza Stark Mode of inheritance for gene: FGD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7465 | COX6A1 | Zornitza Stark Mode of inheritance for gene: COX6A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7464 | JAG2 |
Belinda Chong gene: JAG2 was added gene: JAG2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: JAG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: JAG2 were set to PMID: 33861953 Phenotypes for gene: JAG2 were set to muscular dystrophy Review for gene: JAG2 was set to GREEN Added comment: Whole-exome sequencing identified 13 families with rare homozygous or compound heterozygous JAG2 variants. Bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy. Sources: Literature |
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| Mendeliome v0.7464 | VPS41 |
Kristin Rigbye changed review comment from: "Five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function."; to: "Five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function." "Affected individuals were born after uneventful pregnancies and presented in most cases early in life with developmental delay. Various degrees of ataxia, hypotonia, and dystonia were present in all affected individuals, preventing independent ambulation. Likewise, nystagmus was commonly described. In addition, all affected individuals displayed intellectual disability and speech delay. Two siblings further presented with therapy-resistant epilepsy. No major dysmorphic features were found. In two individuals, retinal pigment alterations were noticed. Brain MRI revealed mild cerebellar atrophy and vermian atrophy without other major structural abnormalities in most affected individuals while in one case (Subject 9) bilateral hyperintensities at the nucleus caudatus area were noted. No hearing or vision problems were noted and in cases where nerve conduction studies were performed, these were normal. Transmission electron microscopy (TEM) on peripheral blood lymphocytes from Subject 2 and lymphoblastoid cells from Subject 3 revealed more multilayered vesicles compared to control cells." |
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| Mendeliome v0.7464 | SIN3B |
Elena Savva gene: SIN3B was added gene: SIN3B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SIN3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SIN3B were set to PMID: 33811806 Phenotypes for gene: SIN3B were set to Syndromic intellectual disability/autism spectrum disorder Review for gene: SIN3B was set to GREEN Added comment: PMID: 33811806 - 9 affected patients, all de novo (2 PTCs, 2 missense, multigenic CNVs) - syndrome hallmarked by intellectual disability, developmental delay, and dysmorphic facial features with variably penetrant ASD, congenital malformations, corpus callosum defects, and impaired growth. - CNVs encompassing the gene have been found Sources: Literature |
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| Mendeliome v0.7464 | DPYSL5 |
Michelle Torres gene: DPYSL5 was added gene: DPYSL5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DPYSL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DPYSL5 were set to 33894126 Phenotypes for gene: DPYSL5 were set to Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities Review for gene: DPYSL5 was set to GREEN Added comment: Nine individuals with brain malformations, including corpus callosum agenesis and/or posterior fossa abnormalities, associated with variable degrees of intellectual disability. The recurrent de novo p.Glu41Lys was found in eight unrelated patients, and a p.Gly47Arg variant was identified in one individual from the first family reported with Ritscher-Schinzel syndrome. Both impaired DPYSL5 function on dendritic outgrowth regulation by preventing the formation of the ternary complex with MAP2 and βIII-tubulin, ultimately leading to abnormal brain development Sources: Literature |
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| Mendeliome v0.7464 | SCD |
Elena Savva gene: SCD was added gene: SCD was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SCD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCD were set to PMID: 33690217; 10899171 Phenotypes for gene: SCD were set to Adrenoleukodystrophy Review for gene: SCD was set to RED Added comment: PMID: 33690217 zebrafish K/O mimics the motor phenotype of ALD zebrafish PMID: 10899171 null mouse was deficient in hepatic cholesterol esters and triglycerides despite the presence of normal activities of acyl-CoA, very low levels of triglycerides Sources: Literature |
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| Mendeliome v0.7460 | BICD2 | Zornitza Stark Mode of inheritance for gene: BICD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7455 | KCNQ5 | Zornitza Stark Mode of inheritance for gene: KCNQ5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7452 | KCNK9 | Zornitza Stark Mode of inheritance for gene: KCNK9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7448 | ATL1 | Zornitza Stark Mode of inheritance for gene: ATL1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7445 | COQ2 | Zornitza Stark Mode of inheritance for gene: COQ2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7442 | COA6 | Zornitza Stark Mode of inheritance for gene: COA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7439 | CARS2 | Zornitza Stark Mode of inheritance for gene: CARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7437 | PPP2R5C |
Sue White gene: PPP2R5C was added gene: PPP2R5C was added to Mendeliome. Sources: Research Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PPP2R5C were set to macrocephaly; intellectual disability Penetrance for gene: PPP2R5C were set to Complete Review for gene: PPP2R5C was set to AMBER Added comment: Emerging unpublished evidence of monoallelic missense variants causing intellectual disability and macrocephaly Sources: Research |
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| Mendeliome v0.7434 | SLX4 | Zornitza Stark Mode of inheritance for gene: SLX4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7430 | SGCE | Zornitza Stark Mode of inheritance for gene: SGCE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7427 | PRKRA | Zornitza Stark Mode of inheritance for gene: PRKRA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7424 | KMT2B | Zornitza Stark Mode of inheritance for gene: KMT2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7421 | CIZ1 | Zornitza Stark Mode of inheritance for gene: CIZ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7417 | NPAS2 | Zornitza Stark Mode of inheritance for gene: NPAS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7413 | PNKD | Zornitza Stark Mode of inheritance for gene: PNKD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7410 | MECR | Zornitza Stark Mode of inheritance for gene: MECR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7407 | HPCA | Zornitza Stark Mode of inheritance for gene: HPCA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7404 | GNAL | Zornitza Stark Mode of inheritance for gene: GNAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7401 | ADCY5 | Zornitza Stark Mode of inheritance for gene: ADCY5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7397 | THAP1 | Zornitza Stark Mode of inheritance for gene: THAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7396 | EIF4G1 | Bryony Thompson Tag for review was removed from gene: EIF4G1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7394 | CHST11 | Zornitza Stark Tag SV/CNV tag was added to gene: CHST11. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7394 | CHST11 |
Zornitza Stark gene: CHST11 was added gene: CHST11 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CHST11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHST11 were set to 26436107; 29514872 Phenotypes for gene: CHST11 were set to Osteochondrodysplasia, brachydactyly, and overlapping malformed digits, MIM# 618167 Review for gene: CHST11 was set to AMBER Added comment: Osteochondrodysplasia, brachydactyly, and overlapping malformed digits (OCBMD) is characterized by bilateral symmetric skeletal defects that primarily affect the limbs. Affected individuals have mild short stature due to shortening of the lower leg bones, as well as hand and foot malformations, predominantly brachydactyly and overlapping digits. Other skeletal defects include scoliosis, dislocated patellae and fibulae, and pectus excavatum. Two unrelated families reported, note one had a homozygous deletion. One family had 10 affected individuals. Sources: Expert Review |
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| Mendeliome v0.7390 | PSMB8 | Zornitza Stark Mode of inheritance for gene: PSMB8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7386 | PPARG | Zornitza Stark Mode of inheritance for gene: PPARG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7383 | POLD1 | Zornitza Stark Mode of inheritance for gene: POLD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7382 | PLIN1 | Zornitza Stark Tag disputed tag was added to gene: PLIN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7380 | PLIN1 | Zornitza Stark Mode of inheritance for gene: PLIN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7376 | PCYT1A | Zornitza Stark Mode of inheritance for gene: PCYT1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7372 | KCNJ6 | Zornitza Stark Mode of inheritance for gene: KCNJ6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7370 | EIF4G1 | Zornitza Stark Tag disputed tag was added to gene: EIF4G1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7369 | EIF4G1 | Zornitza Stark Mode of inheritance for gene: EIF4G1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7367 | EIF4G1 | Bryony Thompson Tag for review tag was added to gene: EIF4G1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7365 | CIDEC | Zornitza Stark Mode of inheritance for gene: CIDEC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7362 | LIG3 |
Zornitza Stark gene: LIG3 was added gene: LIG3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LIG3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIG3 were set to 33855352 Phenotypes for gene: LIG3 were set to gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy Review for gene: LIG3 was set to GREEN Added comment: Three unrelated families and functional data. Sources: Literature |
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| Mendeliome v0.7360 | HNRNPDL |
Bryony Thompson gene: HNRNPDL was added gene: HNRNPDL was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HNRNPDL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPDL were set to 24647604; 31267206; 31995753; 32407983; 32904822; 32367994 Phenotypes for gene: HNRNPDL were set to Muscular dystrophy, limb-girdle, autosomal dominant 3 MIM#609115 Review for gene: HNRNPDL was set to GREEN gene: HNRNPDL was marked as current diagnostic Added comment: At least 5 families reported with either D378H/N, and supporting functional assays demonstrating that these variants affect protein function. No other pathogenic variants have been reported. A VUS has been reported (along with another SETX variant) in an individual with a multi-system disorder, including a metabolic myopathy. Sources: Expert list |
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| Mendeliome v0.7358 | JMJD1C |
Zornitza Stark gene: JMJD1C was added gene: JMJD1C was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JMJD1C were set to 26181491; 32996679 Phenotypes for gene: JMJD1C were set to Intellectual disability Review for gene: JMJD1C was set to GREEN Added comment: Reported in ID cohort (with Rett-like phenotypic overlap) with supporting functional studies (PMID: 26181491). 7 individuals with rare variants identified, and variants demonstrated to be de novo in 2, one with a Rett-like phenotype and the other with ID. Functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. JMJD1C protein shown to be widely expressed in brain regions and that its depletion compromised dendritic activity. Splice-disrupting JMJD1C variant reported in association with learning disability and myoclonic epilepsy (PMID 32996679). Disruption of gene due to balanced translocation (PMID 33591602) implicated in autism spectrum disease phenotype. Sources: Expert Review |
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| Mendeliome v0.7355 | CAVIN1 | Zornitza Stark Mode of inheritance for gene: CAVIN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7352 | CAV1 | Zornitza Stark Mode of inheritance for gene: CAV1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7349 | AFF4 | Zornitza Stark Mode of inheritance for gene: AFF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7346 | GCGR |
Zornitza Stark gene: GCGR was added gene: GCGR was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GCGR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GCGR were set to 19657311; 25695890; 27933176; 30032256; 30294546 Phenotypes for gene: GCGR were set to Mahvash disease, MIM# 619290 Review for gene: GCGR was set to GREEN Added comment: Mahvash disease (MVAH) is caused by inactivating mutations in the glucagon receptor, leading to alpha-cell hyperplasia of the pancreas, hyperglucagonaemia without glucagonoma syndrome, and occasional hypoglycaemia. The disease may lead to glucagonomas and/or primitive neuroectodermal tumours. More than 5 unrelated families reported. Sources: Expert list |
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| Mendeliome v0.7341 | ABCB6 | Zornitza Stark Mode of inheritance for gene: ABCB6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7339 | PRDM15 |
Zornitza Stark gene: PRDM15 was added gene: PRDM15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRDM15 were set to 31950080 Phenotypes for gene: PRDM15 were set to Steroid resistant nephrotic syndrome; Holoprosencephaly Review for gene: PRDM15 was set to AMBER Added comment: Four consanguineous families reported with same homozygous variant, C844Y, shown to be LoF. Syndromic SRNS including HPE, brain malformations, polydactyly, congenital heart disease. Mouse model, extensive functional data focused on the brain phenotype. Two additional homozygous missense identified with isolated SRNS. Sources: Literature |
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| Mendeliome v0.7336 | ZIC2 | Zornitza Stark Mode of inheritance for gene: ZIC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7333 | TGIF1 | Zornitza Stark Mode of inheritance for gene: TGIF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7330 | SIX3 | Zornitza Stark Mode of inheritance for gene: SIX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7327 | DISP1 | Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7323 | TBX3 | Zornitza Stark Mode of inheritance for gene: TBX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7321 | SALL1 | Zornitza Stark Mode of inheritance for gene: SALL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7315 | HELLS | Zornitza Stark Mode of inheritance for gene: HELLS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7312 | ZBTB24 | Zornitza Stark Mode of inheritance for gene: ZBTB24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7309 | CDCA7 | Zornitza Stark Mode of inheritance for gene: CDCA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7305 | XPC | Zornitza Stark Mode of inheritance for gene: XPC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7302 | XPA | Zornitza Stark Mode of inheritance for gene: XPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7299 | RMI2 | Zornitza Stark Mode of inheritance for gene: RMI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7295 | RAD51 | Zornitza Stark Mode of inheritance for gene: RAD51 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7292 | POLH | Zornitza Stark Mode of inheritance for gene: POLH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7287 | MRE11 | Zornitza Stark Mode of inheritance for gene: MRE11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7284 | MPLKIP | Zornitza Stark Mode of inheritance for gene: MPLKIP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7281 | PIK3CD | Zornitza Stark Mode of inheritance for gene: PIK3CD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7278 | GTF2H5 | Zornitza Stark Mode of inheritance for gene: GTF2H5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7275 | GTF2E2 | Zornitza Stark Mode of inheritance for gene: GTF2E2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7271 | FANCL | Zornitza Stark Mode of inheritance for gene: FANCL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7268 | FANCI | Zornitza Stark Mode of inheritance for gene: FANCI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7265 | FANCG | Zornitza Stark Mode of inheritance for gene: FANCG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7262 | FANCF | Zornitza Stark Mode of inheritance for gene: FANCF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7259 | FANCE | Zornitza Stark Mode of inheritance for gene: FANCE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7256 | MDM2 | Zornitza Stark Mode of inheritance for gene: MDM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7250 | NDUFB11 | Zornitza Stark Mode of inheritance for gene: NDUFB11 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7247 | FANCC | Zornitza Stark Mode of inheritance for gene: FANCC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7244 | MFAP5 | Zornitza Stark Mode of inheritance for gene: MFAP5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7240 | FANCB | Zornitza Stark Mode of inheritance for gene: FANCB was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7236 | FANCA | Zornitza Stark Mode of inheritance for gene: FANCA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7233 | ERCC8 | Zornitza Stark Mode of inheritance for gene: ERCC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7230 | GP1BA | Zornitza Stark Mode of inheritance for gene: GP1BA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7225 | ERCC4 | Zornitza Stark Mode of inheritance for gene: ERCC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7222 | ERCC3 | Zornitza Stark Mode of inheritance for gene: ERCC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7218 | SDHA | Zornitza Stark Mode of inheritance for gene: SDHA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7217 | SLC19A1 |
Zornitza Stark gene: SLC19A1 was added gene: SLC19A1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC19A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC19A1 were set to 32276275 Phenotypes for gene: SLC19A1 were set to Megaloblastic anemia, folate-responsive, MIM# 601775 Review for gene: SLC19A1 was set to RED Added comment: Single individual reported with in-frame deletion, some functional data. Sources: Expert list |
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| Mendeliome v0.7214 | ERCC2 | Zornitza Stark Mode of inheritance for gene: ERCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7207 | RORC | Zornitza Stark Mode of inheritance for gene: RORC was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7204 | KCNH1 | Zornitza Stark Mode of inheritance for gene: KCNH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7201 | PLD1 | Zornitza Stark Tag founder tag was added to gene: PLD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7199 | EMC10 | Zornitza Stark Tag founder tag was added to gene: EMC10. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7197 | ITGB3 | Zornitza Stark Mode of inheritance for gene: ITGB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7192 | ADCY6 |
Zornitza Stark changed review comment from: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies. Sources: Literature; to: - PMID: 33820833 (2021) - Further 2 sibs reported with a homozygous c.3346C>T:p.Arg1116Cys variant in the ADCY6 gene. The family was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and IUGR were detected prenatally. Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies. Sources: Literature |
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| Mendeliome v0.7191 | UNC50 |
Arina Puzriakova gene: UNC50 was added gene: UNC50 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UNC50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC50 were set to 29016857; 33820833 Phenotypes for gene: UNC50 were set to Arthrogryposis multiplex congenita Review for gene: UNC50 was set to AMBER Added comment: UNC50 is currently not associated with any phenotype in OMIM (last edited on 02/01/2018) or Gene2Phenotype. - PMID: 29016857 (2017) - Homozygosity mapping of disease loci combined with WES in a single male from a consanguineous family presenting with lethal AMC revealed a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.Cys251Phefs*4). Functional studies in C. elegans showed the variant caused loss of acetylcholine receptor expression in the muscle. - PMID: 33820833 (2021) - Single individual reported with the same homozygous c.750_751del:p.Cys251Phefs*4 variant in UNC50 as previously described. The case was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and tetra ventricular dilation were detected prenatally. -- Note: it isn't definitively clear whether these are different individuals. Both are singleton males born to consanguineous parents, with the same variant and similar phenotype. Also both infants died at 28 w.g. However, the 2021 paper (PMID:33820833) states their patient was selected from a cohort of cases without a molecular diagnosis and indicate the UNC50 gene had already previously been identified in relation to this phenotype, highlighting the earlier paper (PMID:29016857). There is also no mention of tetra ventricular dilation in the first case, so it is likely that these do represent distinct individuals. Additional cases needed to provide clarity. Sources: Literature |
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| Mendeliome v0.7191 | PLCH1 |
Arina Puzriakova gene: PLCH1 was added gene: PLCH1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLCH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLCH1 were set to 33820834 Phenotypes for gene: PLCH1 were set to Holoprosencephaly spectrum; Severe developmental delay; Brain malformations Review for gene: PLCH1 was set to AMBER Added comment: PLCH1 is currently not associated with any phenotype in OMIM (last edited on 16/06/2009) or Gene2Phenotype. - PMID: 33820834 (2021) - Two sibling pairs from two unrelated families with a holoprosencephaly spectrum phenotype and different homozygous PLCH1 variants (c.2065C>T, p.Arg689* and c.4235delA, p.Cys1079ValfsTer16, respectively). One family presented with congenital hydrocephalus, epilepsy, significant developmental delay and a monoventricle or fused thalami; while sibs from the second family had alobar holoprosencephaly and cyclopia. 3/4 individuals also displayed a cleft palate and congenital heart disease. Human embryo immunohistochemistry showed PLCH1 to be expressed in the notorcord, developing spinal cord (in a ventral to dorsal gradient), dorsal root ganglia, cerebellum and dermatomyosome. Sources: Literature |
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| Mendeliome v0.7189 | DDX11 | Zornitza Stark Mode of inheritance for gene: DDX11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7187 | PDIA6 |
Zornitza Stark gene: PDIA6 was added gene: PDIA6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes Review for gene: PDIA6 was set to AMBER Added comment: Amber in view of the good quality functional data. 1 case with asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes. Whole exome sequencing revealed a homozygous frameshift variant in the PDIA6 gene. RNA expression was reduced in a gene dosage‐dependent manner, supporting a loss‐of‐function effect of this variant. Phenotypic correlation with the previously reported mouse model recapitulated the growth defect and delay, early lethality, coagulation, diabetes, immunological, and polycystic kidney disease phenotypes. The phenotype of the current patient is consistent with phenotypes associated with the disruption of PDIA6 and the sensors of UPR in mice and humans. Sources: Literature |
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| Mendeliome v0.7186 | EXOSC1 |
Zornitza Stark gene: EXOSC1 was added gene: EXOSC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EXOSC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOSC1 were set to 33463720 Phenotypes for gene: EXOSC1 were set to Pontocerebellar hypoplasia Review for gene: EXOSC1 was set to RED Added comment: An 8‐months‐old male with developmental delay, microcephaly, subtle dysmorphism, hypotonia, pontocerebellar hypoplasia and delayed myelination. Similarly affected elder sibling succumbed at the age of 4‐years 6‐months. Exome sequencing revealed a homozygous missense variant (c.104C >T, p.Ser35Leu) in EXOSC1. In silico mutagenesis revealed loss of a polar contact with neighbouring Leu37 residue. Quantitative real‐time PCR indicated no appreciable differences in EXOSC1 transcript levels. Immunoblotting and blue native PAGE revealed reduction in the EXOSC1 protein levels and EXO9 complex in the proband, respectively. Of note, bi‐allelic variants in other exosome subunits EXOSC3, EXOSC8 and EXOSC9 have been reported to cause pontocerebellar hypoplasia type 1B, type 1C and type 1D, respectively. Sources: Literature |
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| Mendeliome v0.7182 | UBE4A |
Zornitza Stark gene: UBE4A was added gene: UBE4A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBE4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UBE4A were set to 33420346 Phenotypes for gene: UBE4A were set to Intellectual disability and global developmental delay Review for gene: UBE4A was set to GREEN Added comment: 8 individuals, from 4 unrelated families, with syndromic intellectual disability and global developmental delay (other clinical features included hypotonia, short stature, seizures, and behaviour disorder. Exome sequencing identified biallelic loss-of-function variants in UBE4A in the 4 families, with variants segregating with disease and parents carriers. They demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioural abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals. Sources: Literature |
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| Mendeliome v0.7180 | MAPKAPK5 |
Zornitza Stark gene: MAPKAPK5 was added gene: MAPKAPK5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAPKAPK5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAPKAPK5 were set to 3344202 Phenotypes for gene: MAPKAPK5 were set to Developmental delay, variable brain anomalies, congenital heart defects, dysmorphic Review for gene: MAPKAPK5 was set to GREEN Added comment: 3 individuals from 2 families with severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet. Exome sequencing identified different homozygous truncating variants in MAPKAPK5 in both families, segregating with disease and unaffected parents as carriers. Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization. Sources: Literature |
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| Mendeliome v0.7177 | FAR1 | Zornitza Stark Mode of inheritance for gene: FAR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7173 | GRIA3 | Zornitza Stark Mode of inheritance for gene: GRIA3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7172 | FAT1 |
Ee Ming Wong changed review comment from: - 5 consanguineous families with homozygous frameshift mutations in FAN1 - FAN1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice - in human retinal pigment epithelium (RPE) cells, FAN1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation; to: - 5 consanguineous families with homozygous frameshift mutations in FAT1 - FAT1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice - in human retinal pigment epithelium (RPE) cells, FAT1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation |
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| Mendeliome v0.7172 | SLC17A5 | Zornitza Stark Tag founder tag was added to gene: SLC17A5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7170 | SLC17A5 | Zornitza Stark Mode of inheritance for gene: SLC17A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7167 | SGSH | Zornitza Stark Mode of inheritance for gene: SGSH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7164 | SMPD1 | Zornitza Stark Mode of inheritance for gene: SMPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7158 | PPT1 | Zornitza Stark Mode of inheritance for gene: PPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7155 | NEU1 | Zornitza Stark Mode of inheritance for gene: NEU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7151 | NAGLU | Zornitza Stark Mode of inheritance for gene: NAGLU was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7147 | MIA3 |
Zornitza Stark gene: MIA3 was added gene: MIA3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIA3 were set to 32101163; 33778321 Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269 Review for gene: MIA3 was set to AMBER Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported. Mouse model has absence of bone mineralization. Sources: Expert list |
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| Mendeliome v0.7143 | MCOLN1 | Zornitza Stark Mode of inheritance for gene: MCOLN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7142 | MCOLN1 | Zornitza Stark Tag SV/CNV tag was added to gene: MCOLN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7141 | MANBA | Zornitza Stark Mode of inheritance for gene: MANBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7139 | MAN2B1 | Zornitza Stark Mode of inheritance for gene: MAN2B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7136 | LIPA | Zornitza Stark Mode of inheritance for gene: LIPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7134 | LAMP2 | Zornitza Stark Mode of inheritance for gene: LAMP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7130 | IDS | Zornitza Stark Mode of inheritance for gene: IDS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7127 | VWA1 |
Melanie Marty gene: VWA1 was added gene: VWA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: VWA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VWA1 were set to 33459760; 33693694; 33559681 Phenotypes for gene: VWA1 were set to Hereditary motor neuropathy Review for gene: VWA1 was set to GREEN Added comment: Six different truncating variants identified in 15 affected individuals from six families (biallelic inheritance). Disease manifested in childhood or adulthood with proximal and distal muscle weakness predominantly of the lower limbs. Myopathological and neurophysiological findings were indicative of combined neurogenic and myopathic pathology. Early childhood foot deformity was frequent, but no sensory signs were observed. An additional 17 individuals from 15 families with hereditary motor neuropathy were identified. A 10-bp repeat expansion at the end of exon 1 was observed in 14 families and was homozygous in 10 of them. This mutation, c.62_71dup [p.Gly25Argfs*74], leads to a frameshift that results in a reduction in VWA1 transcript levels via nonsense-mediated decay. Sources: Literature |
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| Mendeliome v0.7121 | TSPOAP1 |
Ain Roesley gene: TSPOAP1 was added gene: TSPOAP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TSPOAP1 were set to 33539324 Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy Penetrance for gene: TSPOAP1 were set to unknown Review for gene: TSPOAP1 was set to GREEN Added comment: 7 affecteds from 3 families (1 consanguineous) 2x null, 1x missense Affecteds with the null variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy while those with the missense p.(Gly1808Ser) presented with isolated adult-onset focal dystonia (mild cognitive impairment noted) mice KO models were investigated Sources: Literature |
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| Mendeliome v0.7121 | CLDN11 |
Melanie Marty gene: CLDN11 was added gene: CLDN11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CLDN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CLDN11 were set to 33313762 Phenotypes for gene: CLDN11 were set to Hypomyelinating leukodystrophy Review for gene: CLDN11 was set to GREEN Added comment: In three unrelated individuals with early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia, 2 different heterozygous de novo stop-loss variants were identified. One of the variants did not lead to a loss of CLDN11 expression on RNA level in fibroblasts indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein. Sources: Literature |
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| Mendeliome v0.7121 | SYK |
Paul De Fazio gene: SYK was added gene: SYK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SYK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SYK were set to 33782605 Phenotypes for gene: SYK were set to Immune dysregulation and systemic inflammation Mode of pathogenicity for gene: SYK was set to Other Review for gene: SYK was set to GREEN gene: SYK was marked as current diagnostic Added comment: 5 unrelated patients with monoallelic missense variants in SYK with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas. 2 patients were confirmed de novo, others were undetermined. Variants exhibited a GoF effect in functional studies. A knock-in mouse model of a patient variant recapitulated aspects of the human disease. Sources: Literature |
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| Mendeliome v0.7121 | NCDN |
Ain Roesley gene: NCDN was added gene: NCDN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NCDN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NCDN were set to 33711248 Phenotypes for gene: NCDN were set to neurodevelopmental delay, intellectual disability, and epilepsy Penetrance for gene: NCDN were set to unknown Review for gene: NCDN was set to GREEN Added comment: 4x families all missense and de novo except for 1 consag family where 3 affecteds were homozygous and carrier parents unaffected ID ranged from mild to severe 3/4 probands had seizures only 3 affecteds had MRI done, with 1 delayed myelination in vitro studies were done Sources: Literature |
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| Mendeliome v0.7119 | SLC5A5 | Zornitza Stark Mode of inheritance for gene: SLC5A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7116 | SLC45A1 | Zornitza Stark Mode of inheritance for gene: SLC45A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7113 | MESP1 |
Zornitza Stark gene: MESP1 was added gene: MESP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MESP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MESP1 were set to 28677747; 28050627; 27185833; 26694203 Phenotypes for gene: MESP1 were set to Congenital heart disease Review for gene: MESP1 was set to AMBER Added comment: Rare/novel variants reported in at least 7 unrelated individuals with congenital heart disease, in-silicos conflicting, familial segregation only available for some (one de novo, three inherited, others unresolved). Functional data implicates gene in cardiac development. Sources: Expert list |
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| Mendeliome v0.7110 | HYAL1 | Zornitza Stark Mode of inheritance for gene: HYAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7104 | HEXB | Zornitza Stark Mode of inheritance for gene: HEXB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7101 | GUSB | Zornitza Stark Mode of inheritance for gene: GUSB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7098 | GNS | Zornitza Stark Mode of inheritance for gene: GNS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7095 | GNPTG | Zornitza Stark Mode of inheritance for gene: GNPTG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7092 | CHD7 | Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7087 | ALDH1A2 | Bryony Thompson Mode of inheritance for gene: ALDH1A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7085 | FBN2 | Zornitza Stark Mode of inheritance for gene: FBN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7082 | MMP20 | Bryony Thompson Mode of inheritance for gene: MMP20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7080 | NDUFB7 |
Bryony Thompson gene: NDUFB7 was added gene: NDUFB7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NDUFB7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFB7 were set to 33502047; 27626371 Phenotypes for gene: NDUFB7 were set to Congenital lactic acidosis; hypertrophic cardiomyopathy Review for gene: NDUFB7 was set to AMBER Added comment: Single patient with a homozygous variant impacting RNA splicing (c.113-10C>G) with intrauterine growth restriction and anaemia, which displayed postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with fatal outcome. Also, a supporting knockout cell line model demonstrating impaired complex I assembly. Sources: Literature |
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| Mendeliome v0.7076 | CDH11 | Zornitza Stark Mode of inheritance for gene: CDH11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7075 | CELA3B |
Bryony Thompson gene: CELA3B was added gene: CELA3B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CELA3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CELA3B were set to 31369399; 33565216 Phenotypes for gene: CELA3B were set to Chronic pancreatitis Mode of pathogenicity for gene: CELA3B was set to Other Review for gene: CELA3B was set to AMBER Added comment: PMID: 33565216 - p.Arg90Cys (c.268C>T) identified in a chronic pancreatitis (also diabetes and pancreatic adenocarcinoma present in some individuals) pedigree. Variant was present in 2 affected individuals and not present in 7 healthy relatives. Also, supporting in vitro functional assays demonstrating gain of function mechanism for R90C and R90L, and supporting mouse model. PMID: 31369399 - p.Arg90Leu (c.269G>T) identified in 4 French chronic pancreatitis cases and 0 controls. However, there are 229 hets in gnomAD v2.1 with this variant. Sources: Literature |
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| Mendeliome v0.7073 | SLC10A1 |
Zornitza Stark gene: SLC10A1 was added gene: SLC10A1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC10A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC10A1 were set to 24867799; 27882152; 28835676; 29290974; 31201272 Phenotypes for gene: SLC10A1 were set to Familial hypercholanemia-2, MIM#619256 Review for gene: SLC10A1 was set to GREEN Added comment: IEM characterised by persistently increased plasma levels of conjugated bile salts apparent from infancy. Most patients are asymptomatic and have no liver dysfunction, although some neonates may have transient jaundice or transiently elevated liver enzymes. These abnormalities improve with age. The bile acid defect can result in impaired absorption of fat-soluble vitamins, including D and K, causing decreased bone mineral density or prolonged prothrobin time (PT). Some variants are recurrent (founder effect likely) but at least 3 different variants reported, mouse model. Sources: Expert list |
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| Mendeliome v0.7070 | GALNS | Zornitza Stark Mode of inheritance for gene: GALNS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7067 | GALC | Zornitza Stark Mode of inheritance for gene: GALC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7063 | FUCA1 | Zornitza Stark Mode of inheritance for gene: FUCA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7060 | CTSD | Zornitza Stark Mode of inheritance for gene: CTSD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7056 | NMNAT1 | Zornitza Stark Mode of inheritance for gene: NMNAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7053 | NMNAT1 |
Zornitza Stark Tag SV/CNV tag was added to gene: NMNAT1. Tag founder tag was added to gene: NMNAT1. |
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| Mendeliome v0.7050 | ZMPSTE24 | Zornitza Stark Mode of inheritance for gene: ZMPSTE24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7046 | EDN1 | Zornitza Stark Mode of inheritance for gene: EDN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7042 | CLN5 | Zornitza Stark Mode of inheritance for gene: CLN5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7039 | CLN3 | Zornitza Stark Mode of inheritance for gene: CLN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7036 | ARSB | Zornitza Stark Mode of inheritance for gene: ARSB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7033 | AGA | Zornitza Stark Mode of inheritance for gene: AGA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7030 | ATCAY | Zornitza Stark Mode of inheritance for gene: ATCAY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7027 | ARAP3 |
Zornitza Stark gene: ARAP3 was added gene: ARAP3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARAP3 were set to 32908855 Phenotypes for gene: ARAP3 were set to Lymphoedema Review for gene: ARAP3 was set to AMBER Added comment: Three unrelated families reported with rare missense variants in this gene as part of a lymphoedema cohort. However, incomplete information regarding segregation and no supporting functional data. Sources: Literature |
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| Mendeliome v0.7024 | RORC | Zornitza Stark Mode of inheritance for gene: RORC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7021 | IL17RC | Zornitza Stark Mode of inheritance for gene: IL17RC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7019 | IL17RA | Zornitza Stark Mode of inheritance for gene: IL17RA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7015 | CARD9 | Zornitza Stark Mode of inheritance for gene: CARD9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7012 | CYP24A1 | Zornitza Stark Mode of inheritance for gene: CYP24A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7007 | ABCB7 | Zornitza Stark Mode of inheritance for gene: ABCB7 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7005 | PORCN | Zornitza Stark Mode of inheritance for gene: PORCN was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7004 | PRIM1 |
Zornitza Stark Tag deep intronic tag was added to gene: PRIM1. Tag founder tag was added to gene: PRIM1. |
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| Mendeliome v0.7004 | PRIM1 |
Zornitza Stark changed review comment from: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature; to: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature |
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| Mendeliome v0.7003 | PRIM1 |
Zornitza Stark changed review comment from: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature; to: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature |
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| Mendeliome v0.7003 | PRIM1 |
Zornitza Stark changed review comment from: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature; to: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature |
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| Mendeliome v0.7003 | PRIM1 |
Zornitza Stark gene: PRIM1 was added gene: PRIM1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRIM1 were set to 33060134 Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950 Review for gene: PRIM1 was set to AMBER Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature |
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| Mendeliome v0.6996 | CYBA | Zornitza Stark Mode of inheritance for gene: CYBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6994 | COPB2 |
Zornitza Stark gene: COPB2 was added gene: COPB2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: COPB2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COPB2 were set to 29036432 Phenotypes for gene: COPB2 were set to Microcephaly 19, primary, autosomal recessive, MIM# 617800 Review for gene: COPB2 was set to RED Added comment: Two sibs with homozygous missense variant in this gene, mice homozygous for this variant had normal brain size however. Mice compound het for null allele and missense variant had some brain features, suggesting the missense variant is hypomorphic. Sources: Expert list |
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| Mendeliome v0.6991 | WDR62 | Zornitza Stark Mode of inheritance for gene: WDR62 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6988 | TRMT10A | Zornitza Stark Mode of inheritance for gene: TRMT10A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6985 | TRAIP | Zornitza Stark Mode of inheritance for gene: TRAIP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6981 | TOP3A | Zornitza Stark Mode of inheritance for gene: TOP3A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6978 | STIL | Zornitza Stark Mode of inheritance for gene: STIL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6973 | STAMBP | Zornitza Stark Mode of inheritance for gene: STAMBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6970 | PCNT | Zornitza Stark Mode of inheritance for gene: PCNT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6967 | NHEJ1 | Zornitza Stark Mode of inheritance for gene: NHEJ1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6964 | NBN | Zornitza Stark Mode of inheritance for gene: NBN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6961 | MSMO1 | Zornitza Stark Mode of inheritance for gene: MSMO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6958 | MCPH1 | Zornitza Stark Mode of inheritance for gene: MCPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6955 | ATP1A3 | Zornitza Stark Mode of inheritance for gene: ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6951 | LARP7 | Zornitza Stark Mode of inheritance for gene: LARP7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6948 | KNL1 | Zornitza Stark Mode of inheritance for gene: KNL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6944 | BAAT | Zornitza Stark Mode of inheritance for gene: BAAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6941 | KIF11 | Zornitza Stark Mode of inheritance for gene: KIF11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6938 | IER3IP1 | Zornitza Stark Mode of inheritance for gene: IER3IP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6935 | EFTUD2 | Zornitza Stark Mode of inheritance for gene: EFTUD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6932 | CEP152 | Zornitza Stark Mode of inheritance for gene: CEP152 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6929 | GNPAT | Zornitza Stark Mode of inheritance for gene: GNPAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6925 | CD4 | Zornitza Stark Mode of inheritance for gene: CD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6922 | TMEM231 | Zornitza Stark Mode of inheritance for gene: TMEM231 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6919 | TMEM216 | Zornitza Stark Mode of inheritance for gene: TMEM216 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6916 | TMEM138 | Zornitza Stark Mode of inheritance for gene: TMEM138 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6913 | TCTN2 | Zornitza Stark Mode of inheritance for gene: TCTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6910 | TCTN1 | Zornitza Stark Mode of inheritance for gene: TCTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6907 | SMCHD1 | Zornitza Stark Mode of pathogenicity for gene: SMCHD1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6904 | TXNL4A | Zornitza Stark Mode of inheritance for gene: TXNL4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6903 | TXNL4A |
Zornitza Stark Tag SV/CNV tag was added to gene: TXNL4A. Tag 5'UTR tag was added to gene: TXNL4A. |
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| Mendeliome v0.6901 | SPINT2 | Zornitza Stark Tag founder tag was added to gene: SPINT2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6901 | SPINT2 | Zornitza Stark changed review comment from: More than 15 unrelated families reported.; to: Well established gene-disease association. PMID 30445423 reviews 34 patients from 26 families: 13 different variants in SPINT2 were seen, including 3 premature termination codons, 2 start codon removals, and 3 canonical splice site variants, supporting loss of function as the pathogenic mechanism. The most commonly observed variant was Y163C, observed in 40 (59%) of 68 disease alleles. Seven unrelated patients with the Y163C mutation had a shared haplotype, suggesting that it is a founder mutation. Choanal atresia (20/34) and keratitis of infantile onset (26/34) were the most common findings. All patients presented with intractable diarrhoea, with onset typically in the first 2 weeks of life. Episodes of intestinal pseudoobstruction sometimes preceded the onset of diarrhoea. Characteristic epithelial tufts on intestinal histology were seen in 13 of the 34 patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6899 | FOXE1 | Zornitza Stark Mode of inheritance for gene: FOXE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6895 | ANO3 | Zornitza Stark Mode of inheritance for gene: ANO3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6893 | IPO8 |
Zornitza Stark gene: IPO8 was added gene: IPO8 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: IPO8 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: IPO8 were set to Loeys-Dietz syndrome-like; cardiovascular, neurologic, skeletal and immunologic abnormalities Review for gene: IPO8 was set to AMBER Added comment: 12 individuals from 9 unrelated families in a cohort submitted for publication with bi-allelic IPO8 variants. Variants were nonsense/splice and some missense. Patients displayed a phenotype reminiscent of Loeys Dietz syndrome that variably combined cardiovascular, neurologic, skeletal and immunologic abnormalities along with dysmorphic features. Western blot on patient cells (4 individuals) showed reduced IPO8 expression. Disruption of IPO8 homologue in zebrafish associated with cardiac anomalies. Transcriptome analysis in zebrafish showed that IPO8-deficient zebrafish had abnormal TGFbeta pathway expression. Sources: Expert Review |
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| Mendeliome v0.6889 | FAM20C | Zornitza Stark Mode of inheritance for gene: FAM20C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6886 | POLR3A | Zornitza Stark Tag deep intronic tag was added to gene: POLR3A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6884 | ANKS6 | Zornitza Stark Mode of inheritance for gene: ANKS6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6879 | CLDN2 | Zornitza Stark Mode of inheritance for gene: CLDN2 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6876 | HSF2BP |
Zornitza Stark gene: HSF2BP was added gene: HSF2BP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HSF2BP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HSF2BP were set to 32845237 Phenotypes for gene: HSF2BP were set to Premature ovarian failure, OMIM#619245 Review for gene: HSF2BP was set to RED Added comment: Single family reported where homozygous missense variant segregated with POF in three sisters. Sources: Expert list |
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| Mendeliome v0.6873 | COL4A6 | Zornitza Stark Mode of inheritance for gene: COL4A6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6868 | MED12 | Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6865 | BMPR2 | Zornitza Stark Mode of pathogenicity for gene: BMPR2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6864 | BMPR2 | Zornitza Stark Mode of inheritance for gene: BMPR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6861 | ZNF711 | Zornitza Stark Mode of inheritance for gene: ZNF711 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6858 | SLC35A2 | Zornitza Stark Mode of inheritance for gene: SLC35A2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6857 | SLC35A2 | Zornitza Stark Tag somatic tag was added to gene: SLC35A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6857 | MEF2A | Zornitza Stark Mode of inheritance for gene: MEF2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6852 | FN1 | Zornitza Stark Mode of inheritance for gene: FN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6851 | IL37 |
Zornitza Stark gene: IL37 was added gene: IL37 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IL37 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL37 were set to 33674380 Phenotypes for gene: IL37 were set to Infantile inflammatory bowel disease Review for gene: IL37 was set to RED Added comment: Single family reported with homozygous truncating variant this gene and infantile-onset of IBD, some functional data. Sources: Literature |
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| Mendeliome v0.6848 | CHRDL1 | Zornitza Stark Mode of inheritance for gene: CHRDL1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6846 | HDL2 |
Bryony Thompson STR: HDL2 was added STR: HDL2 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: HDL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: HDL2 were set to 20301701 Phenotypes for STR: HDL2 were set to Huntington disease-like 2 MIM#606438 Review for STR: HDL2 was set to GREEN STR: HDL2 was marked as clinically relevant Added comment: NM_001271604.2:c.431CTG[X] or NM_020655.4:c.382+760CTG[X] In an alternatively spliced exon, the repeat can be transcribed in both directions, leading to CUG (more common) or CAG (less common) repeat-containing transcripts. While a dominant RNA toxic effect may occur, the repeat expansion also reduces levels of the Junctophilin-3 protein Normal: ≤28 repeats Questionable significance: 29-39 repeats, mutable normal or reduced penetrance included Full penetrance: ≥40 repeats Sources: Expert list |
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| Mendeliome v0.6843 | DM2 |
Bryony Thompson STR: DM2 was added STR: DM2 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: DM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: DM2 were set to 20301639; 29325606 Phenotypes for STR: DM2 were set to Myotonic dystrophy 2 MIM#602668 Review for STR: DM2 was set to GREEN STR: DM2 was marked as clinically relevant Added comment: HGVS nomenclature: NM_003418.4:c.-14-833_-14-830[X] Toxic gain of function RNA expected mechanism of disease Normal: ≤30 uninterrupted CCTG repeats, 11-26 CCTG repeats with any GCTC or TCTG interruptions Unknown significance (normal vs. mutable): 27-29 CCTG repeats Mutable normal (premutation) alleles. ~30-~54 CCTG repeats Unknown significance (premutation vs pathogenic): ~55-74 CCTG repeats Pathogenic: ~75-11,000 CCTG repeats Sources: Expert list |
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| Mendeliome v0.6840 | DM1 |
Bryony Thompson STR: DM1 was added STR: DM1 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: DM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: DM1 were set to 20301344; 29325606 Phenotypes for STR: DM1 were set to Myotonic dystrophy 1 MIM#160900 Review for STR: DM1 was set to GREEN STR: DM1 was marked as clinically relevant Added comment: HGVS nomenclature: NM_001081560.2:c.*224_*226CTG[X] RNA toxic gain of function is mechanism of disease Premutation: 35-49 repeats, no clinical signs Mild: 50-~150 repeats, age of onset 20-70 yrs, clinical signs - cataracts, mild myotonia Classic: ~100-~1,000 repeats, age of onset 10-30 yrs, clinical signs - weakness, myotonia, cataracts, balding, cardiac arrhythmia Congenital: >1,000 repeats, age of onset birth-10 yrs , clinical signs - infantile hypotonia, respiratory deficits, intellectual disability, classic signs in adults Sources: Expert list |
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| Mendeliome v0.6837 | SCA17 |
Bryony Thompson STR: SCA17 was added STR: SCA17 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA17 were set to 20301611; 29325606 Phenotypes for STR: SCA17 were set to Spinocerebellar ataxia 17 MIM#607136 Review for STR: SCA17 was set to GREEN STR: SCA17 was marked as clinically relevant Added comment: NM_003194.4:c.172_174[X] Mechanism of disease expected to be gain of function Normal: ≤ 40 CAG/CAA repeats Reduced-penetrance: 41-48 CAG/CAA repeats, individual may or may not develop symptoms. Full-penetrance: ≥49 CAG/CAA repeats Sources: Expert list |
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| Mendeliome v0.6834 | SCA12 |
Bryony Thompson STR: SCA12 was added STR: SCA12 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA12 were set to 29325606; 20301381 Phenotypes for STR: SCA12 were set to Spinocerebellar ataxia 12 MIM#604326 Review for STR: SCA12 was set to GREEN STR: SCA12 was marked as clinically relevant Added comment: NM_181675.3:c.27CAG[X] Uncertain if CAG repeat encodes polyglutamine or instead effects expression of specific splice variants of the encoded phosphatase Normal: ≤32 repeats Reduced penetrance: ~40-66 repeats Full penetrance: ≥66 repeats Sources: Expert list |
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| Mendeliome v0.6831 | SCA36 |
Bryony Thompson STR: SCA36 was added STR: SCA36 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA36 were set to 25101480 Phenotypes for STR: SCA36 were set to Spinocerebellar ataxia 36 MIM#614153 Review for STR: SCA36 was set to GREEN STR: SCA36 was marked as clinically relevant Added comment: NM_006392.3:c.3+71GGCCTG[X] Toxic RNA effect is suggested mechanism of disease Normal: 3-14 repeats Uncertain significance: 15-650 repeats Pathogenic: ≥650 repeats Sources: Expert list |
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| Mendeliome v0.6828 | SCA37 |
Bryony Thompson STR: SCA37 was added STR: SCA37 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA37 were set to 28686858; 31145571 Phenotypes for STR: SCA37 were set to Spinocerebellar ataxia 37 MIM#615945 Review for STR: SCA37 was set to GREEN STR: SCA37 was marked as clinically relevant Added comment: NC_000001.10:g.57832716_57832797ins[(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90] Located in a 5'UTR intron, flanked by (ATTTT)n on both sides Non-pathogenic allele: (ATTTT)7–400 Pathogenic allele: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90] Sources: Expert list |
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| Mendeliome v0.6825 | SCA31 |
Bryony Thompson STR: SCA31 was added STR: SCA31 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA31 were set to 19878914; 31755042 Phenotypes for STR: SCA31 were set to Spinocerebellar ataxia 31 MIM#117210 Review for STR: SCA31 was set to GREEN STR: SCA31 was marked as clinically relevant Added comment: Complex repeat insertion (TGGAA)n, (TAGAA)n, (TAAAA)n, (TAAAATAGAA)n, TGGAA is present only in affected cases. Sequencing showed that the insertion consisted of a preceding TCAC sequence, and 3 pentanucleotide repeat components (TGGAA)n, (TAGAA)n, and (TAAAA)n in all patients tested. 2.5-3.8 KB insertion is associated with disease and RNA toxicity expected to be mechanism of disease Normal and pathogenic cut-offs are based on animal model experiments (PMID: 31755042) Sources: Expert list |
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| Mendeliome v0.6822 | SCA7 |
Bryony Thompson STR: SCA7 was added STR: SCA7 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA7 were set to 29325606; 20301433 Phenotypes for STR: SCA7 were set to Spinocerebellar ataxia 7 MIM#164500 Review for STR: SCA7 was set to GREEN STR: SCA7 was marked as clinically relevant Added comment: NM_000333.3:c.89_91AGC[X] Gain of function mechanism of disease Normal: ≤27 repeats Mutable normal: 28-33 repeats, meiotically unstable, but not associated with an abnormal phenotype. Pathogenic reduced penetrance: 34-36 repeats, when manifestations occur, they are more likely to be later onset and milder than average Pathogenic full penetrance: 37-460 repeats Sources: Expert list |
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| Mendeliome v0.6819 | SCA3 |
Bryony Thompson STR: SCA3 was added STR: SCA3 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA3 were set to 20301375; 29325606 Phenotypes for STR: SCA3 were set to Machado-Joseph disease MIM#109150; Spinocerebellar ataxia type 3 Review for STR: SCA3 was set to GREEN STR: SCA3 was marked as clinically relevant Added comment: NM_004993.5:c.886_888CAG[X] Toxic aggregation and mislocalization in neurons is mechanism of disease Normal: ≤44 repeats, mostly <31 repeats Intermediate: 45-59 repeats, some intermediate alleles are not associated with classic clinical features of SCA3 Pathogenic (full penetrance): ≥60 repeats Sources: Expert list |
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| Mendeliome v0.6816 | SCA2 |
Bryony Thompson STR: SCA2 was added STR: SCA2 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA2 were set to 29325606; 20301452 Phenotypes for STR: SCA2 were set to Spinocerebellar ataxia 2 MIM#183090 Review for STR: SCA2 was set to GREEN STR: SCA2 was marked as clinically relevant Added comment: NM_002973.3:c.496_498CAG[X] Toxic protein aggregation is mechanism of disease Benign: ≤31 repeats (homozygous 31/31 repeats reported for recessive SCA2) Uncertain: 32 repeats ALS risk allele: 30-32 repeats Reduced penetrance: 33-34 repeats, may not develop symptoms or only very late in life Full penetrance: ≥35 repeats Interruption of a CAG expanded allele by a CAA repeat does not mitigate the pathogenicity of the repeat size, but may enhance the meiotic stability of the repeat Sources: Expert list |
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| Mendeliome v0.6813 | SCA10 |
Bryony Thompson STR: SCA10 was added STR: SCA10 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA10 were set to 20301354 Phenotypes for STR: SCA10 were set to Spinocerebellar ataxia 10 MIM#603516 Review for STR: SCA10 was set to GREEN STR: SCA10 was marked as clinically relevant Added comment: NM_013236.2:c.1430+54822ATTCT[X] Toxic RNA gain-of-function mechanism of disease Normal alleles: 10-32 ATTCT repeats Alleles of questionable significance: 33-280 ATTCT repeats Reduced-penetrance alleles: 33-850 repeats Full-penetrance alleles: 800-4,500 ATTCT repeats Sources: Expert list |
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| Mendeliome v0.6810 | INPP4A |
Zornitza Stark gene: INPP4A was added gene: INPP4A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INPP4A were set to 31978615; 31938306; 25338135; 20011524 Phenotypes for gene: INPP4A were set to Intellectual disability Review for gene: INPP4A was set to AMBER Added comment: Two families reported with bi-allelic variants and a neurological phenotype. Supportive mouse model and expression data. Sources: Literature |
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| Mendeliome v0.6808 | SATB1 | Zornitza Stark edited their review of gene: SATB1: Added comment: Kohlschutter-Tonz syndrome-like (KTZSL) is characterized by global developmental delay with moderately to severely impaired intellectual development, poor or absent speech, and delayed motor skills. Although the severity of the disorder varies, many patients are nonverbal and have hypotonia with inability to sit or walk. Early-onset epilepsy is common and may be refractory to treatment, leading to epileptic encephalopathy and further interruption of developmental progress. Most patients have feeding difficulties with poor overall growth and dysmorphic facial features, as well as significant dental anomalies resembling amelogenesis imperfecta. This phenotype was reported in 28 patients (patients 13 to 40, PMID 33513338), including 9 patients from 3 families. Most variants were de novo, though some were inherited, suggestive of incomplete penetrance and variable expressivity.; Changed phenotypes: Developmental delay with dysmorphic facies and dental anomalies, MIM# 619228, Kohlschutter-Tonz syndrome-like, MIM# 619229 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6806 | SATB1 | Zornitza Stark Mode of pathogenicity for gene: SATB1 was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6803 | MKS1 | Zornitza Stark Mode of inheritance for gene: MKS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6801 | FLII |
Zornitza Stark gene: FLII was added gene: FLII was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FLII was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FLII were set to 32870709 Phenotypes for gene: FLII were set to Dilated cardiomyopathy Review for gene: FLII was set to AMBER Added comment: Two unrelated families reported with homozygous missense variants. Emerging evidence. Sources: Literature |
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| Mendeliome v0.6799 | RHBDF1 |
Zornitza Stark gene: RHBDF1 was added gene: RHBDF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RHBDF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RHBDF1 were set to 32870709 Phenotypes for gene: RHBDF1 were set to Dilated cardiomyopathy Review for gene: RHBDF1 was set to AMBER Added comment: Three families reported with homozygous variants in this gene and onset of DCM in infancy/childhood. Two of the families had the same truncating variant, indicative of founder effect, and one family had a homozygous missense variant. Sources: Literature |
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| Mendeliome v0.6797 | MYLK3 |
Zornitza Stark gene: MYLK3 was added gene: MYLK3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYLK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709 Phenotypes for gene: MYLK3 were set to Dilated cardiomyopathy Review for gene: MYLK3 was set to AMBER Added comment: Two families reported with mono-allelic variants (one extension, one frameshift), and three consanguineous families reported with bi-allelic variants (two hmz frameshift, one hmz missense). Supportive mouse models. Sources: Literature |
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| Mendeliome v0.6795 | NRAP |
Zornitza Stark gene: NRAP was added gene: NRAP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NRAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRAP were set to 33534821; 30384889; 28611399; 32870709 Phenotypes for gene: NRAP were set to Dilated cardiomyopathy Review for gene: NRAP was set to GREEN Added comment: Twenty unrelated families reported with childhood onset DCM. Sources: Literature |
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| Mendeliome v0.6793 | MPEG1 |
Zornitza Stark gene: MPEG1 was added gene: MPEG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MPEG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MPEG1 were set to 33224153; 33692780; 28422754 Phenotypes for gene: MPEG1 were set to Immunodeficiency 77, MIM# 619223 Review for gene: MPEG1 was set to GREEN Added comment: Immunodeficiency-77 (IMD77) is an immunologic disorder characterized by recurrent and persistent polymicrobial infections with multiple unusual organisms. Skin and pulmonary infections are the most common, consistent with increased susceptibility to epithelial cell infections. The age at onset is highly variable: some patients have recurrent infections from childhood, whereas others present in late adulthood. The limited number of reported patients are all female, suggesting incomplete penetrance or a possible sex-influenced trait. Patient cells, mainly macrophages, show impaired killing of intracellular bacteria and organisms, including nontubercular mycobacteria, although there is also impaired killing of other organisms, such as Pseudomonas, Candida, and Aspergillus. Four individuals reported, functional data, including animal model. Sources: Expert list |
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| Mendeliome v0.6789 | INPP5E | Zornitza Stark Mode of inheritance for gene: INPP5E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6786 | CSPP1 | Zornitza Stark Mode of inheritance for gene: CSPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6783 | CEP41 | Zornitza Stark Mode of inheritance for gene: CEP41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6781 | SCA1 |
Bryony Thompson STR: SCA1 was added STR: SCA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA1 were set to 29325606; 20301363 Phenotypes for STR: SCA1 were set to Spinocerebellar ataxia 1 MIM#164400 STR: SCA1 was marked as clinically relevant Added comment: NM_000332.3:c.589_591CAG[X] Toxic protein aggregation is mechanism of disease Normal: ≤35 CAG repeats or 36-44 CAG repeats with CAT interruptions Mutable normal (intermediate): 36-38 CAG repeats without CAT interruptions Full-penetrance: ≥39 CAG repeats without CAT interruptions or ≥46 uninterrupted CAG repeats with CAT interruptions and additional CAGs Sources: Expert list |
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| Mendeliome v0.6777 | PSENEN | Bryony Thompson Mode of inheritance for gene: PSENEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6773 | ESCO2 | Zornitza Stark Mode of inheritance for gene: ESCO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6769 | ALDH1L2 |
Naomi Baker gene: ALDH1L2 was added gene: ALDH1L2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ALDH1L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALDH1L2 were set to PMID: 31341639; 33168096 Phenotypes for gene: ALDH1L2 were set to pruritic ichthyosis, severe diffuse hypomyelination seen on MRI, and abnormal lipid peaks Review for gene: ALDH1L2 was set to RED Added comment: Individual reported with bialleleic ALDH1L2 variants (non-canonical splice and a frameshift mutation), who also has a de novo hemizygous RPS6KA3 frameshift mutation. Authors state that not all features of the individual could be explained by the RPS6KA3 variant, and that consideration of Coffin-Lowry sysndrome was only made after identification of the RPS6KA3 variant. Therefore individual has there is a blended phenotype of Coffin–Lowry syndrome and Sjögren–Larsson syndrome. From functional studies authors propose that the ALDH1L2 loss induces mitochondrial dysfunction due to reduced NADPH and increased oxidative stress (PMID: 31341639). Knockout mouse model was viable and did not show an apparent phenotype, however metabolomic analysis showed vastly changed metabotypes in the liver and plasma in these mice suggesting channeling of fatty acids away from β-oxidation. Authors therefore postulate that the role of ALDH1L2 in the lipid metabolism explains why the loss of this enzyme is associated with neuro-cutaneous disease. Sources: Literature |
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| Mendeliome v0.6769 | FAM57B | Zornitza Stark Tag new gene name tag was added to gene: FAM57B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6768 | FAM57B |
Zornitza Stark gene: FAM57B was added gene: FAM57B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FAM57B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM57B were set to 33077892 Phenotypes for gene: FAM57B were set to Cone–rod dystrophy; Maculopathy Review for gene: FAM57B was set to GREEN Added comment: 4 patients with cone-rod dystrophy or maculopathy from 3 families, with LOF pathogenic variants in TLCD3B (ceramide synthase gene). Ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. Variants segregated with disease. TLCD3B showed high expression in the adult retina with higher expression in the macular than in the peripheral region. Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina. Sources: Literature |
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| Mendeliome v0.6763 | TAOK2 |
Bryony Thompson gene: TAOK2 was added gene: TAOK2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TAOK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TAOK2 were set to 28385331; 29467497 Phenotypes for gene: TAOK2 were set to Generalized verrucosis; abnormal T cell activation Review for gene: TAOK2 was set to AMBER Added comment: PMID: 28385331 - A single consanguineous family with generalized verrucosis and abnormal T cell activation, and a homozygous missense (p.R700C), with some assays on patient fibroblasts. PMID: 29467497 - One of the several genes in the 16p11.2 microdeletion region associated with autism. Taok2 heterozygous and knockout mice had gene dosage-dependent impairments in cognition, anxiety, social interaction, brain size, and neural connectivity. 3 de novo variants and 3 predicted loss of function variants identified in 6 unrelated autism cases. 2 of the de novo variants have supporting functional assays, but 1 of them co-occurs in an individual with a CHD8 frameshift. 1 of the predicted loss of function variants was also identified in the unaffected father and sibling. Sources: Literature |
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| Mendeliome v0.6760 | CC2D2A | Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6756 | INVS | Zornitza Stark Mode of inheritance for gene: INVS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6754 | ZCCHC8 |
Bryony Thompson gene: ZCCHC8 was added gene: ZCCHC8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZCCHC8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZCCHC8 were set to 31488579 Phenotypes for gene: ZCCHC8 were set to Pulmonary fibrosis Review for gene: ZCCHC8 was set to AMBER Added comment: A missense variant (P186L) segregates over 3 generations in a single family, and supporting in vitro assays and mouse model. Sources: Literature |
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| Mendeliome v0.6751 | KDM5B | Zornitza Stark Mode of inheritance for gene: KDM5B was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6748 | TPP2 | Zornitza Stark Mode of inheritance for gene: TPP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6744 | DOCK7 | Zornitza Stark Mode of inheritance for gene: DOCK7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6742 | UBAP1 |
Zornitza Stark changed review comment from: PMID 31696996: Five unrelated families reported with childhood-onset HSP. A recurrent two‐base pair deletion (c.426_427delGA, p.K143Sfs*15) in the UBAP1 gene was found in four families, and a similar variant (c.475_476delTT, p.F159*) was detected in a fifth family. The variant was confirmed to be de novo in two families and inherited from an affected parent in two other families. RNA studies performed in lymphocytes from one patient with the de novo c.426_427delGA variant demonstrated escape of nonsense‐mediated decay of the UBAP1 mutant transcript, suggesting the generation of a truncated protein. Both variants identified are predicted to result in truncated proteins losing the capacity of binding to ubiquitinated proteins, hence appearing to exhibit a dominant‐negative effect on the normal function of the endosome‐specific endosomal sorting complexes required for the transport‐I complex.; to: PMID 31696996: Five unrelated families reported with childhood-onset HSP. A recurrent two‐base pair deletion (c.426_427delGA, p.K143Sfs*15) in the UBAP1 gene was found in four families, and a similar variant (c.475_476delTT, p.F159*) was detected in a fifth family. The variant was confirmed to be de novo in two families and inherited from an affected parent in two other families. RNA studies performed in lymphocytes from one patient with the de novo c.426_427delGA variant demonstrated escape of nonsense‐mediated decay of the UBAP1 mutant transcript, suggesting the generation of a truncated protein. Both variants identified are predicted to result in truncated proteins losing the capacity of binding to ubiquitinated proteins, hence appearing to exhibit a dominant‐negative effect on the normal function of the endosome‐specific endosomal sorting complexes required for the transport‐I complex. PMID 32934340: additional 7 families. Median age of onset 10yrs. |
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| Mendeliome v0.6740 | RTN2 | Zornitza Stark Mode of inheritance for gene: RTN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6737 | NIPA1 | Zornitza Stark Mode of inheritance for gene: NIPA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6734 | DDHD1 | Zornitza Stark Mode of inheritance for gene: DDHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6727 | AP5Z1 | Zornitza Stark Mode of inheritance for gene: AP5Z1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6725 | COPB1 |
Zornitza Stark gene: COPB1 was added gene: COPB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COPB1 were set to 33632302 Phenotypes for gene: COPB1 were set to Severe intellectual disability; variable microcephaly; cataracts Review for gene: COPB1 was set to AMBER Added comment: Two unrelated families, some supportive functional data. Sources: Literature |
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| Mendeliome v0.6721 | SLC1A4 | Zornitza Stark Mode of inheritance for gene: SLC1A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6720 | SLC1A4 | Zornitza Stark Tag founder tag was added to gene: SLC1A4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6719 | TFG | Zornitza Stark Mode of inheritance for gene: TFG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6716 | WDR45B | Zornitza Stark Mode of inheritance for gene: WDR45B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6713 | REEP2 | Zornitza Stark Mode of inheritance for gene: REEP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6710 | NT5C2 | Zornitza Stark Mode of inheritance for gene: NT5C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6707 | HACE1 | Zornitza Stark Mode of inheritance for gene: HACE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6704 | NKX6-2 | Zornitza Stark Mode of inheritance for gene: NKX6-2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6701 | ARPC1B | Zornitza Stark Mode of inheritance for gene: ARPC1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6697 | KDM5C | Zornitza Stark Mode of inheritance for gene: KDM5C was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6694 | ENTPD1 | Zornitza Stark Mode of inheritance for gene: ENTPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6691 | C12orf65 | Zornitza Stark Mode of inheritance for gene: C12orf65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6690 | C12orf65 | Zornitza Stark Tag new gene name tag was added to gene: C12orf65. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6688 | C19orf12 | Zornitza Stark Mode of inheritance for gene: C19orf12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6685 | CYP2U1 | Zornitza Stark Mode of inheritance for gene: CYP2U1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6684 | IFRD1 |
Zornitza Stark gene: IFRD1 was added gene: IFRD1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: IFRD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IFRD1 were set to 29362493 Phenotypes for gene: IFRD1 were set to Hereditary spastic paraplegia; peripheral neuropathy; ataxia Review for gene: IFRD1 was set to RED Added comment: A variant segregated with slowly progressing gait ataxia, pyramidal tract signs and peripheral neuropathy in three siblings from a single Chinese family. No functional analyses of the variant has been conducted. The variant (c.514 A>G, p.I172V) is too common (0.3%) for a dominant condition in the African population in gnomAD. Sources: Expert Review |
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| Mendeliome v0.6684 | IFRD1 |
Zornitza Stark gene: IFRD1 was added gene: IFRD1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: IFRD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IFRD1 were set to 29362493 Phenotypes for gene: IFRD1 were set to Hereditary spastic paraplegia; peripheral neuropathy; ataxia Review for gene: IFRD1 was set to RED Added comment: A variant segregated with slowly progressing gait ataxia, pyramidal tract signs and peripheral neuropathy in three siblings from a single Chinese family. No functional analyses of the variant has been conducted. The variant (c.514 A>G, p.I172V) is too common (0.3%) for a dominant condition in the African population in gnomAD. Sources: Expert Review |
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| Mendeliome v0.6683 | KLC4 |
Zornitza Stark gene: KLC4 was added gene: KLC4 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KLC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KLC4 were set to 26423925 Phenotypes for gene: KLC4 were set to Complicated hereditary spastic paraplegia Review for gene: KLC4 was set to RED Added comment: Single family reported. Sources: Expert Review |
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| Mendeliome v0.6680 | AP4M1 | Zornitza Stark Mode of inheritance for gene: AP4M1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6677 | ADAMTS13 | Zornitza Stark Mode of inheritance for gene: ADAMTS13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6674 | AP4S1 | Zornitza Stark Mode of inheritance for gene: AP4S1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6671 | AIMP1 | Zornitza Stark Mode of inheritance for gene: AIMP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6669 | UBA1 | Zornitza Stark Tag somatic tag was added to gene: UBA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6665 | CC2D1A | Zornitza Stark Mode of inheritance for gene: CC2D1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6662 | ZAP70 | Zornitza Stark Mode of pathogenicity for gene: ZAP70 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6661 | ZAP70 | Zornitza Stark Mode of inheritance for gene: ZAP70 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6658 | CST3 | Zornitza Stark Mode of inheritance for gene: CST3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6656 | CST3 | Zornitza Stark Tag founder tag was added to gene: CST3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6654 | NR3C1 | Zornitza Stark Mode of inheritance for gene: NR3C1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6647 | CDT1 | Zornitza Stark Mode of inheritance for gene: CDT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6646 | DYRK1A | Zornitza Stark Tag SV/CNV tag was added to gene: DYRK1A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6644 | CDK5RAP2 | Zornitza Stark Mode of inheritance for gene: CDK5RAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6637 | DONSON | Zornitza Stark Mode of inheritance for gene: DONSON was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6631 | PGK1 | Zornitza Stark Mode of inheritance for gene: PGK1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6628 | PGM1 | Zornitza Stark Mode of inheritance for gene: PGM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6627 | PHKA1 | Zornitza Stark Mode of inheritance for gene: PHKA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6624 | PHKA1 | Zornitza Stark Mode of inheritance for gene: PHKA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6621 | PHKB | Zornitza Stark Mode of inheritance for gene: PHKB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6618 | PHKG2 | Zornitza Stark Mode of inheritance for gene: PHKG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6615 | PYGL | Zornitza Stark Mode of inheritance for gene: PYGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6612 | NHLRC1 | Zornitza Stark Mode of inheritance for gene: NHLRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6611 | LDHA | Zornitza Stark Tag SV/CNV tag was added to gene: LDHA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6609 | LDHA | Zornitza Stark Mode of inheritance for gene: LDHA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6606 | RPL18 |
Zornitza Stark gene: RPL18 was added gene: RPL18 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RPL18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPL18 were set to 28280134; 32075953 Phenotypes for gene: RPL18 were set to Diamond-Blackfan anemia 18, MIM# 618310 Review for gene: RPL18 was set to AMBER Added comment: One family and a zebrafish model. Sources: Expert list |
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| Mendeliome v0.6605 | RPS15A |
Zornitza Stark gene: RPS15A was added gene: RPS15A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RPS15A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPS15A were set to 27909223 Phenotypes for gene: RPS15A were set to Diamond-Blackfan anemia 20, MIM# 618313 Review for gene: RPS15A was set to RED Added comment: Single family reported. Sources: Expert list |
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| Mendeliome v0.6604 | RPL35 |
Zornitza Stark gene: RPL35 was added gene: RPL35 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RPL35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPL35 were set to 28280134 Phenotypes for gene: RPL35 were set to Diamond-Blackfan anemia 19, MIM# 618312 Review for gene: RPL35 was set to RED Added comment: Single family reported. Sources: Expert list |
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| Mendeliome v0.6601 | RPS7 | Zornitza Stark Mode of inheritance for gene: RPS7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6598 | RPS26 | Zornitza Stark Mode of inheritance for gene: RPS26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6595 | RPS24 | Zornitza Stark Mode of inheritance for gene: RPS24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6591 | RPS19 | Zornitza Stark Mode of inheritance for gene: RPS19 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6589 | SIAH1 |
Arina Puzriakova gene: SIAH1 was added gene: SIAH1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SIAH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SIAH1 were set to 32430360 Phenotypes for gene: SIAH1 were set to Developmental delay; Infantile hypotonia; Dysmorphic features; Laryngomalacia Review for gene: SIAH1 was set to GREEN Added comment: - PMID: 32430360 (2021) - Five unrelated individuals with shared features of developmental delay, infantile hypotonia, dysmorphic features and laryngomalacia. All had speech delay and where cognitive assessment was age appropriate individuals exhibited learning difficulties. Trio WES revealed distinct de novo variants in SIAH1. In vitro assays demonstrated that SIAH1 mutants induce loss of Wnt stimulatory activity. Sources: Literature |
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| Mendeliome v0.6586 | RPL5 | Zornitza Stark Mode of inheritance for gene: RPL5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6585 | RPL35A | Zornitza Stark Tag SV/CNV tag was added to gene: RPL35A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6583 | RPL35A | Zornitza Stark Mode of inheritance for gene: RPL35A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6582 | SYCP2L |
Arina Puzriakova gene: SYCP2L was added gene: SYCP2L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SYCP2L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SYCP2L were set to 32303603 Phenotypes for gene: SYCP2L were set to Premature ovarian insufficiency Review for gene: SYCP2L was set to AMBER Added comment: - PMID: 32303603 (2021) - Two unrelated individuals with premature ovarian insufficiency and homozygous variants (c.150_151del (p.Ser52Profs*7), c.999A>G (p.Ile333Met)) in SYCP2L. In vitro assays revealed that mutant SYCP2L proteins induced mislocalisation and reduced expression. Sycp2l knockout mice exhibit accelerated reproductive ageing. Sources: Literature |
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| Mendeliome v0.6580 | RPL27 | Zornitza Stark Mode of inheritance for gene: RPL27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6576 | RPL11 | Zornitza Stark Mode of inheritance for gene: RPL11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6575 | PSAP | Zornitza Stark Mode of inheritance for gene: PSAP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6570 | CLCN4 | Zornitza Stark Mode of inheritance for gene: CLCN4 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6567 | EN1 |
Zornitza Stark changed review comment from: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. Sources: Literature; to: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. An additional fourth individual had cerebellar hypoplasia in addition to the skeletal phenotype, and a bi-allelic LoF variant. Sources: Literature |
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| Mendeliome v0.6567 | EN1 |
Zornitza Stark Tag SV/CNV tag was added to gene: EN1. Tag 5'UTR tag was added to gene: EN1. |
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| Mendeliome v0.6566 | EN1 |
Zornitza Stark gene: EN1 was added gene: EN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EN1 were set to 33568816 Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217 Review for gene: EN1 was set to GREEN Added comment: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. Sources: Literature |
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| Mendeliome v0.6557 | MKRN3 | Zornitza Stark Mode of inheritance for gene: MKRN3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6556 | MKRN3 |
Zornitza Stark Tag SV/CNV tag was added to gene: MKRN3. Tag 5'UTR tag was added to gene: MKRN3. |
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| Mendeliome v0.6556 | ACSL5 |
Zornitza Stark gene: ACSL5 was added gene: ACSL5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ACSL5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACSL5 were set to 33191500 Phenotypes for gene: ACSL5 were set to severe FTT (no OMIM #) Review for gene: ACSL5 was set to RED Added comment: 6 individuals of a large consanguineous family presented in the neonatal period with recurrent vomiting and diarrhea, leading to severe FTT. Autozygosity mapping and WES identified homozygous variant (c.1358C>A:p.(Thr453Lys) in ACSL5. Segregated with affected individuals. Functional in vitro analysis of the ACSL5 variant by immunofluorescence, western blotting and enzyme assay suggested that Thr453Lys is a loss‐of‐function mutation without any remaining activity. Affected individuals were treated with total parenteral nutrition or medium‐chain triglyceride‐based formula restricted in long‐chain triglycerides. They responded well and follow up suggests that treatment is only required during early life. Sources: Literature |
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| Mendeliome v0.6553 | GDF5 | Zornitza Stark Mode of inheritance for gene: GDF5 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6550 | KIDINS220 | Zornitza Stark Mode of inheritance for gene: KIDINS220 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6545 | MYO3A | Zornitza Stark Mode of inheritance for gene: MYO3A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6542 | COL9A3 | Zornitza Stark Mode of inheritance for gene: COL9A3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6540 | DLK1 |
Zornitza Stark gene: DLK1 was added gene: DLK1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: DLK1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: DLK1 were set to 28324015; 30462238 Phenotypes for gene: DLK1 were set to central precocious puberty Review for gene: DLK1 was set to GREEN Added comment: PMID: 30462238 "three frameshift mutations of DLK1 (p.Gly199Alafs*11, p.Val271Cysfs*14, and p.Pro160Leufs*50) in five women from three families with CPP. Segregation analysis was consistent with the maternal imprinting of DLK1". PMID: 28324015 single large family, only affected females, central precocious puberty all carrying paternally inherited LOF variant (del/dup of 5'UTR and exon 1) absent DLK1 expression in all affected. Unclear if males affected as none reported to date. Sources: Expert Review |
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| Mendeliome v0.6538 | EIF5A |
Zornitza Stark gene: EIF5A was added gene: EIF5A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF5A were set to 33547280 Phenotypes for gene: EIF5A were set to Intellectual disability; microcephaly; dysmorphism Review for gene: EIF5A was set to GREEN Added comment: 7 unrelated individuals reported with de novo variants in this gene and variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Sources: Literature |
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| Mendeliome v0.6536 | POLRMT |
Zornitza Stark gene: POLRMT was added gene: POLRMT was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POLRMT was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: POLRMT were set to 33602924 Phenotypes for gene: POLRMT were set to Mitochondrial disorder; intellectual disability; hypotonia Review for gene: POLRMT was set to GREEN Added comment: 8 individuals from 7 families reported. 5 families with bi-allelic variants and 2 with heterozygous variants. Affected individuals presented with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype. Sources: Literature |
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| Mendeliome v0.6533 | PERP | Zornitza Stark Mode of inheritance for gene: PERP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6528 | KARS | Zornitza Stark Mode of inheritance for gene: KARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6526 | APOO |
Arina Puzriakova gene: APOO was added gene: APOO was added to Mendeliome. Sources: Literature Mode of inheritance for gene: APOO was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: APOO were set to 32439808 Phenotypes for gene: APOO were set to Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour Review for gene: APOO was set to RED Added comment: - PMID: 32439808 (2021) - Three generation family with c.350T>C variant in APOO, encoding a component of the MICOS complex which plays a role in maintaining inner mitochondrial membrane architecture. Phenotypes include fatigue and muscle weakness (6/8), learning difficulties and cognitive impairment (4/8), and increased blood lactate (2/8). Four individuals were asymptomatic carriers, including one male (authors indicate variability in female carriers was due to skewed X-inactivation, although skewing studies were inconclusive in some cases). Variability in clinical presentation suggests reduced penetrance or possible contribution of additional factors. Functional studies showed altered MICOS assembly and abnormalities in mitochondria ultrastructure in patient-derived fibroblasts. Knockdown studies in Drosophila and yeast demonstrated mitochondrial structural and functional deficiencies. Sources: Literature |
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| Mendeliome v0.6526 | AMH | Zornitza Stark Tag founder tag was added to gene: AMH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6524 | ECE1 | Zornitza Stark Mode of inheritance for gene: ECE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6520 | AMH | Seb Lunke Mode of inheritance for gene: AMH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6517 | PAX4 | Zornitza Stark Mode of inheritance for gene: PAX4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6514 | PCBD1 | Zornitza Stark Mode of inheritance for gene: PCBD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6511 | SPTAN1 | Zornitza Stark Mode of inheritance for gene: SPTAN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6506 | NLRP3 | Zornitza Stark Mode of pathogenicity for gene: NLRP3 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6503 | IRF4 | Bryony Thompson Mode of inheritance for gene: IRF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6501 | PCBD1 |
Michelle Torres edited their review of gene: PCBD1: Added comment: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes. PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY; Changed phenotypes: MODY, Hyperphenylalaninemia, BH4-deficient, D 264070 |
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| Mendeliome v0.6500 | SPTAN1 | Alison Yeung Mode of inheritance for gene: SPTAN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6498 | PSAP | Seb Lunke Mode of inheritance for gene: PSAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6494 | SPTAN1 | Melanie Marty changed review comment from: 13 affected individuals from 4 families reported (nonsense variants) with AD distal hereditary motor neuropathy. Variable penetrance was noted and phenotype severity differs greatly between patients; to: 13 affected individuals from 4 families reported (nonsense variants) with AD distal hereditary motor neuropathy. Variable penetrance was noted and phenotype severity differs greatly between patients. Functional studies show NMD and reduced protein levels in patient cells. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6494 | PCBD1 |
Michelle Torres changed review comment from: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes. PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY; to: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes. PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY |
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| Mendeliome v0.6490 | PCBD1 |
Michelle Torres changed review comment from: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes with features similar to dominantly inherited HNF1A-diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY; to: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes. PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY |
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| Mendeliome v0.6490 | EPAS1 | Seb Lunke Mode of pathogenicity for gene: EPAS1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6489 | NLRP3 | Alison Yeung Mode of inheritance for gene: NLRP3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6488 | EPAS1 | Seb Lunke Mode of inheritance for gene: EPAS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6486 | MED27 |
Alison Yeung gene: MED27 was added gene: MED27 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MED27 were set to 33443317 Phenotypes for gene: MED27 were set to Intellectual disability; cerebellar hypoplasia; dystonia Review for gene: MED27 was set to GREEN gene: MED27 was marked as current diagnostic Added comment: 16 patients from 11 families with balletic variants Sources: Literature |
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| Mendeliome v0.6485 | ACTL9 |
Elena Savva gene: ACTL9 was added gene: ACTL9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ACTL9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACTL9 were set to PMID: 33626338 Phenotypes for gene: ACTL9 were set to Fertilization failure; male infertility Review for gene: ACTL9 was set to GREEN Added comment: Three families with homozygous pathogenic variants (two missense, one PTC). Single affected in each family. Functional analysis from patients shows all sperm had morphological defects, protein had reduced binding to ACTL7A All variants very rare in gnomAD. Sources: Literature |
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| Mendeliome v0.6485 | MAST2 |
Elena Savva gene: MAST2 was added gene: MAST2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAST2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MAST2 were set to PMID: 33465109 Phenotypes for gene: MAST2 were set to Thrombophilia; venous thrombosis Review for gene: MAST2 was set to RED Added comment: Single missense identified in a family with venous thrombosis and thrombophilia. Missense variant reviewed by in silicos only. Shown to affect regulation of TFP1 and SERPINE1 gene expression. RNAi of MAST2 followed by RNAseq showed expression changes in many downstream targets Sources: Literature |
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| Mendeliome v0.6483 | AGPS | Zornitza Stark Mode of inheritance for gene: AGPS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6480 | BANF1 | Zornitza Stark Mode of inheritance for gene: BANF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6476 | FOXP2 | Zornitza Stark Mode of inheritance for gene: FOXP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6473 | GLI3 | Zornitza Stark Mode of inheritance for gene: GLI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6469 | KIF22 | Zornitza Stark Mode of inheritance for gene: KIF22 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6467 | ANKZF1 |
Bryony Thompson gene: ANKZF1 was added gene: ANKZF1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: ANKZF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ANKZF1 were set to 28302725 Phenotypes for gene: ANKZF1 were set to Infantile-onset inflammatory bowel disease Review for gene: ANKZF1 was set to AMBER Added comment: Two unrelated cases (1 homozygous and 1 compound heterozygous), and supporting in vitro and yeast assays indicating that loss-of-function mutations in ANKZF1 result in deregulation of mitochondrial integrity. Sources: Other |
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| Mendeliome v0.6465 | ANGPT1 |
Bryony Thompson gene: ANGPT1 was added gene: ANGPT1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: ANGPT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ANGPT1 were set to 28601681; 24852101; 30689269; 10617467; 8980224 Phenotypes for gene: ANGPT1 were set to Hereditary angioedema Review for gene: ANGPT1 was set to AMBER Added comment: A missense variant (A119S) identified in 4 affected individuals in a single family. Supportive data in patient cells, functional assays of the variant, and animal models (both overexpression and null) for the gene. Sources: Other |
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| Mendeliome v0.6463 | CLTCL1 |
Bryony Thompson changed review comment from: PMID: 26068709 - Three siblings in a single consanguineous family with congenital insensitivity to pain, inability to feel touch, and cognitive delay and a homozygous rare missense variant (Glu330Lys - no homozygotes in gnomAD v2.1). In vitro functional assays of the variant suggested a deleterious effect on the protein. Additionally cellular assays suggested a role for the gene in neural crest development and in the genesis of pain and touch sensing neurons. PMID: 29402896 - more in depth functional assays and proteomic analyses suggesting a role for the protein in regulating sensory neuron differentiation in the human peripheral system Other reports of associations with limited evidence: PMID: 22511880 - Identified as a candidate gene in an autism study, but the homozygous variant (reported as R125C, but actually R1165C) has 40 homozygotes in gnomAD v2.1. And many of the other compound heterozygous candidate variants in the study are too common in gnomAD v2.1, with many homozygotes present. The missense reported in the pain insensitivity family Glu330Lys was reported with another rare missense variant (Glu1310Lys) in one of the autism cases, but no other phenotype information was provided. PMID: 31354784 - a single case with infantile spasm reported with compound het missense (Met1316Val & Arg1165Cys), but both are very common in gnomAD v2.1 with 33,000 and 40 homozygotes, respectively. Sources: Literature; to: PMID: 26068709 - Three siblings in a single consanguineous family with congenital insensitivity to pain, inability to feel touch, and cognitive delay and a homozygous rare missense variant (Glu330Lys - no homozygotes in gnomAD v2.1). In vitro functional assays of the variant suggested a deleterious effect on the protein. Additionally cellular assays suggested a role for the gene in neural crest development and in the genesis of pain and touch sensing neurons. PMID: 29402896 - more in depth functional assays and proteomic analyses suggesting a role for the protein in regulating sensory neuron differentiation in the human peripheral system. Other reports of associations with limited evidence: PMID: 22511880 - Identified as a candidate gene in an autism study, but the homozygous variant (reported as R125C, but actually R1165C) has 40 homozygotes in gnomAD v2.1. And many of the other compound heterozygous candidate variants in the study are too common in gnomAD v2.1, with many homozygotes present. The missense reported in the pain insensitivity family Glu330Lys was reported with another rare missense variant (Glu1310Lys) in one of the autism cases, but no other phenotype information was provided. PMID: 31354784 - a single case with infantile spasm reported with compound het missense (Met1316Val & Arg1165Cys), but both are very common in gnomAD v2.1 with 33,000 and 40 homozygotes, respectively. Sources: Literature |
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| Mendeliome v0.6463 | CLTCL1 |
Bryony Thompson gene: CLTCL1 was added gene: CLTCL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CLTCL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLTCL1 were set to 26068709; 29402896; 22511880; 31354784 Phenotypes for gene: CLTCL1 were set to Congenital insensitivity to pain Review for gene: CLTCL1 was set to AMBER Added comment: PMID: 26068709 - Three siblings in a single consanguineous family with congenital insensitivity to pain, inability to feel touch, and cognitive delay and a homozygous rare missense variant (Glu330Lys - no homozygotes in gnomAD v2.1). In vitro functional assays of the variant suggested a deleterious effect on the protein. Additionally cellular assays suggested a role for the gene in neural crest development and in the genesis of pain and touch sensing neurons. PMID: 29402896 - more in depth functional assays and proteomic analyses suggesting a role for the protein in regulating sensory neuron differentiation in the human peripheral system Other reports of associations with limited evidence: PMID: 22511880 - Identified as a candidate gene in an autism study, but the homozygous variant (reported as R125C, but actually R1165C) has 40 homozygotes in gnomAD v2.1. And many of the other compound heterozygous candidate variants in the study are too common in gnomAD v2.1, with many homozygotes present. The missense reported in the pain insensitivity family Glu330Lys was reported with another rare missense variant (Glu1310Lys) in one of the autism cases, but no other phenotype information was provided. PMID: 31354784 - a single case with infantile spasm reported with compound het missense (Met1316Val & Arg1165Cys), but both are very common in gnomAD v2.1 with 33,000 and 40 homozygotes, respectively. Sources: Literature |
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| Mendeliome v0.6458 | G6PC | Zornitza Stark Mode of inheritance for gene: G6PC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6455 | NMNAT2 |
Bryony Thompson gene: NMNAT2 was added gene: NMNAT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NMNAT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NMNAT2 were set to 31132363; 25271157; 20126265 Phenotypes for gene: NMNAT2 were set to polyneuropathy; erythromelalgia Review for gene: NMNAT2 was set to AMBER Added comment: A single family with siblings with a homozygous variant that confers a partial loss of function. Strong supporting functional evidence that the gene plays a key role in axonal survival. Sources: Literature |
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| Mendeliome v0.6452 | CCT5 | Bryony Thompson Mode of inheritance for gene: CCT5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6445 | C1GALT1C1 | Bryony Thompson Tag somatic tag was added to gene: C1GALT1C1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6435 | ALDOA | Zornitza Stark Mode of inheritance for gene: ALDOA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6432 | RDH5 | Zornitza Stark Mode of inheritance for gene: RDH5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6429 | RPGRIP1 | Zornitza Stark Mode of inheritance for gene: RPGRIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6426 | IRX4 | Zornitza Stark Mode of inheritance for gene: IRX4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6422 | AKAP6 | Zornitza Stark Mode of inheritance for gene: AKAP6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6419 | ASCC3 |
Bryony Thompson gene: ASCC3 was added gene: ASCC3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ASCC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASCC3 were set to 21937992; https://doi.org/10.1016/j.xhgg.2021.100024 Phenotypes for gene: ASCC3 were set to Neuromuscular syndrome; congenital myopathy Review for gene: ASCC3 was set to GREEN Added comment: 11 individuals from 7 unrelated families with homozygous (missense) or compound heterozygous variants (missense with a presumed LoF variant or 2 missense, no biallelic LoF) with a neurologic phenotype that ranges from severe developmental delay to muscle fatigue. Sources: Literature |
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| Mendeliome v0.6408 | CRYM | Zornitza Stark Mode of inheritance for gene: CRYM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6405 | HARS | Zornitza Stark Mode of inheritance for gene: HARS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6400 | PMVK |
Zornitza Stark gene: PMVK was added gene: PMVK was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: PMVK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PMVK were set to 26202976 Phenotypes for gene: PMVK were set to Porokeratosis 1, multiple types, MIM# 175800 Review for gene: PMVK was set to GREEN Added comment: At least 9 individuals reported. Sources: Expert Review |
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| Mendeliome v0.6398 | MVD |
Zornitza Stark gene: MVD was added gene: MVD was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MVD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MVD were set to 30942823; 33491095 Phenotypes for gene: MVD were set to Porokeratosis 7, multiple types, MIM# 614714 Review for gene: MVD was set to GREEN Added comment: Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. At least 5 individuals reported. Sources: Expert list |
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| Mendeliome v0.6394 | SHROOM3 |
Zornitza Stark gene: SHROOM3 was added gene: SHROOM3 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SHROOM3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SHROOM3 were set to 32621286 Phenotypes for gene: SHROOM3 were set to Anencephaly; cleft lip and palate Review for gene: SHROOM3 was set to AMBER Added comment: Animal model and other functional data link SHROOM3 to neural tube development. Single family reported with bi-allelic LoF in a fetus with anencephaly and CL/P. Sources: Expert Review |
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| Mendeliome v0.6390 | MSL3 | Zornitza Stark Mode of inheritance for gene: MSL3 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6387 | TOE1 | Zornitza Stark Mode of inheritance for gene: TOE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6384 | VRK1 | Zornitza Stark Mode of inheritance for gene: VRK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6381 | SPTBN2 | Zornitza Stark Mode of inheritance for gene: SPTBN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6378 | SEPSECS | Zornitza Stark Mode of inheritance for gene: SEPSECS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6375 | ITPR1 | Zornitza Stark Mode of inheritance for gene: ITPR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6372 | EXOSC8 | Zornitza Stark Mode of inheritance for gene: EXOSC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6371 | EXOSC8 | Zornitza Stark Tag founder tag was added to gene: EXOSC8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6369 | EXOSC3 | Zornitza Stark Mode of inheritance for gene: EXOSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6368 | CLP1 | Zornitza Stark Tag founder tag was added to gene: CLP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6366 | CLP1 | Zornitza Stark Mode of inheritance for gene: CLP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6363 | CHMP1A | Zornitza Stark Mode of inheritance for gene: CHMP1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6360 | BRF1 | Zornitza Stark Mode of inheritance for gene: BRF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6357 | DHODH | Zornitza Stark Mode of inheritance for gene: DHODH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6354 | ITGB4 | Zornitza Stark Mode of inheritance for gene: ITGB4 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6351 | LAMA3 | Zornitza Stark Mode of inheritance for gene: LAMA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6348 | LAMB3 | Zornitza Stark Mode of inheritance for gene: LAMB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6345 | LAMC2 | Zornitza Stark Mode of inheritance for gene: LAMC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6343 | KRT5 | Zornitza Stark Mode of inheritance for gene: KRT5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6338 | ITGA6 | Zornitza Stark Mode of inheritance for gene: ITGA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6335 | ITGA3 | Zornitza Stark Mode of inheritance for gene: ITGA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6332 | FERMT1 | Zornitza Stark Mode of inheritance for gene: FERMT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6329 | EXPH5 | Zornitza Stark Mode of inheritance for gene: EXPH5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6327 | COL7A1 | Zornitza Stark Mode of inheritance for gene: COL7A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6324 | IGSF1 | Zornitza Stark Mode of inheritance for gene: IGSF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6320 | FSTL5 |
Eleanor Williams gene: FSTL5 was added gene: FSTL5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FSTL5 was set to Unknown Publications for gene: FSTL5 were set to 33105483 Phenotypes for gene: FSTL5 were set to isolated club-foot; iTEV; Talipes equinovarus Review for gene: FSTL5 was set to RED Added comment: PMID: 33105483 - Khanshour et al 20201 - GWAS study of isolated Talipes equinovarus (clubfoot, iTEV) identified an associated locus within FSTL5. They show that Fstl5 is expressed in the embryonic hindlimb in bats, chicks and mice. However, Fstl5 was expressed more highly in neural tissues in mice, and rats lacking Fstl5 showed no gross developmental malformations. Conditional overexpression of Fstl5 in osteochondroprogenitors resulted in sexually dimorphic differences in skeletal development in mice. Sources: Literature |
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| Mendeliome v0.6320 | NCOA3 |
Eleanor Williams gene: NCOA3 was added gene: NCOA3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NCOA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NCOA3 were set to 33326993 Phenotypes for gene: NCOA3 were set to non-syndromic hearing loss Review for gene: NCOA3 was set to RED Added comment: PMID: 33326993 - Salazar da Silva et al 2020 - report a 5 generation Brazilian family with 15 individuals with non-syndromic, bilateral and progressive hearing loss. Using linkage analysis and then exome sequencing they identified a heterozygous variant in NCOA3 (NM_181659, c.2810C > G; p.Ser937Cys) that was found in the 7 analysed affected individuals. It was also found in 4 unaffected individuals but they are within the range of onset of hearing loss observed in the family. Expression of nco3 was found in the inner ear of mice and zebrafish. ncoa3-/- zebrafish showed subtle alterations in cartilage, mineral density and abnormal adult swimming behaviour, which may suggest the mechanism of pathogenicity. Sources: Literature |
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| Mendeliome v0.6318 | CFHR3 | Zornitza Stark Mode of inheritance for gene: CFHR3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6315 | CFHR1 | Zornitza Stark Mode of inheritance for gene: CFHR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6309 | SCARB1 | Bryony Thompson Mode of inheritance for gene: SCARB1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6305 | CETP | Bryony Thompson Mode of inheritance for gene: CETP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6303 | DMGDH | Bryony Thompson Mode of inheritance for gene: DMGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6297 | SHPK |
Bryony Thompson gene: SHPK was added gene: SHPK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SHPK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SHPK were set to 25647543; 27604308 Phenotypes for gene: SHPK were set to Sedoheptulokinase deficiency MIM#617213 Review for gene: SHPK was set to AMBER Added comment: 2 unrelated cases reported, with elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense variant. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Due to inconsistency in phenotypes, likely SHPK deficiency is a benign disorder. Sources: Literature |
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| Mendeliome v0.6295 | PNLIP |
Bryony Thompson gene: PNLIP was added gene: PNLIP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PNLIP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNLIP were set to 31977950; 25862608; 24262094; 27604308 Phenotypes for gene: PNLIP were set to Pancreatic lipase deficiency MIM#614338; disorders of lipid and lipoprotein metabolism Review for gene: PNLIP was set to GREEN Added comment: 4 cases from 2 unrelated families, with supporting biochemical assays in patient cells and cellular-based assays. The cases have decreased absorption of dietary fat and greasy voluminous stools, but apparent normal development and an overall good state of health. Sources: Literature |
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| Mendeliome v0.6294 | TDO2 |
Zornitza Stark gene: TDO2 was added gene: TDO2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TDO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TDO2 were set to 28285122; 27604308 Phenotypes for gene: TDO2 were set to Hypertryptophanemia MIM#600627; Disorders of histidine, tryptophan or lysine metabolism Review for gene: TDO2 was set to RED Added comment: Single case reported, biochemical phenotype of hypertryptophanemia and hyperserotoninemia does not appear to have significant clinical consequences Sources: Expert list |
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| Mendeliome v0.6291 | SUGCT | Zornitza Stark Mode of inheritance for gene: SUGCT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6287 | SLC36A2 | Zornitza Stark Mode of inheritance for gene: SLC36A2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6283 | SARDH | Zornitza Stark Mode of inheritance for gene: SARDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6279 | OPLAH | Zornitza Stark Mode of inheritance for gene: OPLAH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6277 | OPLAH | Zornitza Stark Tag disputed tag was added to gene: OPLAH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6275 | KHK | Zornitza Stark Mode of inheritance for gene: KHK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6271 | HAL | Zornitza Stark Mode of inheritance for gene: HAL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6266 | DCXR |
Zornitza Stark gene: DCXR was added gene: DCXR was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DCXR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DCXR were set to 22042873 Phenotypes for gene: DCXR were set to Pentosuria MIM#260800; Disorders of pentose metabolism Review for gene: DCXR was set to AMBER Added comment: At least 9 Ashkenazi Jewish probands reported. The condition is clinically benign. Sources: Expert list |
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| Mendeliome v0.6263 | CTH | Zornitza Stark Mode of inheritance for gene: CTH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6259 | ACSF3 | Zornitza Stark Mode of inheritance for gene: ACSF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6255 | PHGDH | Zornitza Stark Mode of inheritance for gene: PHGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6251 | PNP | Zornitza Stark Mode of inheritance for gene: PNP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6248 | PNPLA2 | Zornitza Stark Mode of inheritance for gene: PNPLA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6245 | ESRP2 | Zornitza Stark Mode of inheritance for gene: ESRP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6241 | ACBD5 | Zornitza Stark Mode of inheritance for gene: ACBD5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6238 | SAR1B | Zornitza Stark Mode of inheritance for gene: SAR1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6235 | SC5D | Zornitza Stark Mode of inheritance for gene: SC5D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6232 | SLC39A14 | Zornitza Stark Mode of inheritance for gene: SLC39A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6229 | SLC46A1 | Zornitza Stark Mode of inheritance for gene: SLC46A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6226 | ST3GAL3 | Zornitza Stark Mode of inheritance for gene: ST3GAL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6224 | DDX58 | Zornitza Stark Mode of pathogenicity for gene: DDX58 was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6222 | DDX58 | Zornitza Stark Mode of pathogenicity for gene: DDX58 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6221 | DDX58 | Zornitza Stark edited their review of gene: DDX58: Added comment: Prasov et al. 2021 (PMID: 33495304) - A heterozygous DDX58 variant (c.1529A>T) was identified in 5 individuals from 2 unrelated families from different ethnic backgrounds. Phenotypes varied with some being severely affected by systemic features and others solely with glaucoma.Functional analysis demonstrated the variant confers a dominant gain-of-function effect on interferon activity.; Changed mode of pathogenicity: Other; Changed publications: 25620203, 33495304 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6207 | WBP11 |
Eleanor Williams gene: WBP11 was added gene: WBP11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: WBP11 were set to 33276377 Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems Review for gene: WBP11 was set to GREEN Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies. Sources: Literature |
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| Mendeliome v0.6207 | TTF2 |
Zornitza Stark gene: TTF2 was added gene: TTF2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: TTF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TTF2 were set to 30022773 Phenotypes for gene: TTF2 were set to congenital hypothyroidism, thyroid dysgenesis, No OMIM # Review for gene: TTF2 was set to RED Added comment: 1 case only Sources: Expert Review |
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| Mendeliome v0.6205 | DUOXA1 |
Zornitza Stark gene: DUOXA1 was added gene: DUOXA1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: DUOXA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: DUOXA1 were set to 29650690 Phenotypes for gene: DUOXA1 were set to congenital hypothyroidism, No OMIM # Review for gene: DUOXA1 was set to AMBER Added comment: 12 cases, but digenic model with variants in other genes Sources: Expert Review |
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| Mendeliome v0.6203 | DUOX1 |
Zornitza Stark gene: DUOX1 was added gene: DUOX1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: DUOX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: DUOX1 were set to 29650690 Phenotypes for gene: DUOX1 were set to congenital hypothyroidism, No OMIM # Review for gene: DUOX1 was set to AMBER Added comment: 11 cases, but digenic model, with variants in other genes. Sources: Expert Review |
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| Mendeliome v0.6200 | TTF1 | Zornitza Stark Mode of inheritance for gene: TTF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6197 | CDCA8 |
Zornitza Stark gene: CDCA8 was added gene: CDCA8 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CDCA8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CDCA8 were set to 28025328; 29546359 Phenotypes for gene: CDCA8 were set to Congenital hypothyroidism, thyroid dysgenesis, no OMIM # Mode of pathogenicity for gene: CDCA8 was set to Other Review for gene: CDCA8 was set to GREEN Added comment: 4 families (1 with bilallelic variants [parent affected as HTZ], 3 with monoallelic variants) with functional evidence of variants. GREEN for mono allelic, RED for biallelic. Sources: Expert Review |
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| Mendeliome v0.6195 | DNAJC30 |
Zornitza Stark gene: DNAJC30 was added gene: DNAJC30 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAJC30 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAJC30 were set to 33465056 Phenotypes for gene: DNAJC30 were set to Leber Hereditary Optic Neuropathy Review for gene: DNAJC30 was set to GREEN Added comment: 33 individuals from 29 families had homozygous DNAJC30 missense variants. Three different variants identified (one responsible for most cases). All three variants absent from gnomAD. Incomplete penetrance and male predominance in affected individuals both typical of LHON due to mtDNA mutations. All 3 variants in the J domain of the protein. Functional evidence. Sources: Literature |
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| Mendeliome v0.6193 | PCDH19 | Zornitza Stark Mode of inheritance for gene: PCDH19 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6192 | SLC7A6OS |
Zornitza Stark gene: SLC7A6OS was added gene: SLC7A6OS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC7A6OS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC7A6OS were set to 33085104 Phenotypes for gene: SLC7A6OS were set to Progressive myoclonus epilepsy Review for gene: SLC7A6OS was set to RED Added comment: Two unrelated families reported with same homozygous splice site variant, shared haplotype (founder effect). Limited functional data. Sources: Literature |
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| Mendeliome v0.6191 | TLR8 | Zornitza Stark Tag somatic tag was added to gene: TLR8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6190 | TLR8 |
Zornitza Stark gene: TLR8 was added gene: TLR8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TLR8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: TLR8 were set to 33512449 Phenotypes for gene: TLR8 were set to Immunodeficiency; bone marrow failure Mode of pathogenicity for gene: TLR8 was set to Other Review for gene: TLR8 was set to GREEN Added comment: Six unrelated males reported with a phenotype comprising neutropaenia, infections, lymphoproliferation, humoral immune defects, and in some cases bone marrow failure. Three different variants reported, the variant was somatic in 5/6 individuals. GoF mechanism demonstrated. Sources: Literature |
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| Mendeliome v0.6187 | PIGF |
Paul De Fazio changed review comment from: The same homozygous missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated. Rated Red as the two families are likely to be related (founder mutation?). Sources: Literature; to: The same homozygous missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness - only one of the two had seizures (GTCS), the other was 14mo and noted to have tonic posturing. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated by flow cytometry and a rescue assay. Alkaline phosphatase in both individuals was normal. Rated Red as the two families are likely to be related (founder mutation?). Sources: Literature |
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| Mendeliome v0.6187 | PIGF |
Paul De Fazio changed review comment from: The same missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated. Rated Red as the two families are likely to be related (founder mutation?). Sources: Literature; to: The same homozygous missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated. Rated Red as the two families are likely to be related (founder mutation?). Sources: Literature |
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| Mendeliome v0.6187 | PIGF |
Paul De Fazio changed review comment from: Identified in 2 individuals with a phenotype similar to DOORS (syndrome Sources: Literature; to: The same missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated. Rated Red as the two families are likely to be related (founder mutation?). Sources: Literature |
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| Mendeliome v0.6187 | PIGF |
Paul De Fazio gene: PIGF was added gene: PIGF was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PIGF was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGF were set to 33386993 Phenotypes for gene: PIGF were set to Glycosylphosphatidylinositol\ deficiency, onychodystrophy, osteodystrophy, intellectual disability, and seizures Review for gene: PIGF was set to RED gene: PIGF was marked as current diagnostic Added comment: Identified in 2 individuals with a phenotype similar to DOORS (syndrome Sources: Literature |
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| Mendeliome v0.6187 | BRWD1 |
Paul De Fazio gene: BRWD1 was added gene: BRWD1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BRWD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BRWD1 were set to 33389130 Phenotypes for gene: BRWD1 were set to Asthenoteratozoospermia, likely primary ciliary dyskinesia Review for gene: BRWD1 was set to GREEN gene: BRWD1 was marked as current diagnostic Added comment: Biallelic missense variants reported in 3 unrelated individuals. Apart from asthenoteratozoospermia, all 3 had PCD or "PCD-likely" symptoms of re-occurring airway infections, bronchiectasis, and rhinosinusitis. One individual had situs inversus. Studies on cells from one indivdidual showed abnormal respiratory cilia structure. BRWD1 staining was absent from respiratory cilia in this individual (present in controls). Rated Green as there are three unrelated individuals reported. Sources: Literature |
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| Mendeliome v0.6184 | HIRA |
Paul De Fazio gene: HIRA was added gene: HIRA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HIRA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HIRA were set to 33417013; 28135719; 25363760 Phenotypes for gene: HIRA were set to Neurodevelopmental disorder Review for gene: HIRA was set to GREEN gene: HIRA was marked as current diagnostic Added comment: Two unrelated patients with different de novo loss of function variants identified in PMID 33417013: Individual 1: intragenic deletion, phenotype included psychomotor retardation, ID, growth retardation, microcephaly, and facial features reminiscent of 22q deletion syndrome. Individual 2: canonical splice variant, phenotype mostly confined to ASD Another two de novo variants were identified in the literature by the authors of that paper, one stop-gain (DDD study, PMID 28135719) and one missense (large autism cohort, PMID 25363760). PMID 33417013 also showed that HIRA knockdown in mice results in neurodevelopmental abnormalities. Rated Green due to 4 unrelated individuals (albeit 2 in large cohort studies) and a mouse model. NB: HIRA is within the common 22q deletion region. Sources: Literature |
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| Mendeliome v0.6182 | POLR3B | Zornitza Stark Mode of inheritance for gene: POLR3B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6179 | EYA3 |
Paul De Fazio gene: EYA3 was added gene: EYA3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EYA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: EYA3 were set to 33475861 Phenotypes for gene: EYA3 were set to Oculo-auriculo-vertebral spectrum (OAVS) Review for gene: EYA3 was set to RED gene: EYA3 was marked as current diagnostic Added comment: 3 individuals with OAVS from two unrelated families with the same missense variant, p.(Asn358Ser). Variant has 20 heterozygotes in gnomAD. Unaffected carriers in both families were also identified - unknown if incomplete penetrance or nonsegregation. Functional studies indicate the variant increases protein half life, and gene knockdown in zebrafish had an effect on craniofacial development. Rated Red due to both families sharing the variant and uncertainty about incomplete penetrance versus nonsegregation. Sources: Literature |
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| Mendeliome v0.6178 | HEY2 |
Zornitza Stark gene: HEY2 was added gene: HEY2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HEY2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: HEY2 were set to 32820247 Phenotypes for gene: HEY2 were set to congenital heart defects and thoracic aortic aneurysms Review for gene: HEY2 was set to RED Added comment: A very large family affected by CHD and familial thoracic aortic aneurysms. Trio genome sequencing was carried out in an index patient with critical CHD, and family members had either exome or Sanger sequencing. Identified homozygous loss-of-function variant (c.318_319delAG, p.G108*) in HEY2 in 3 individuals in family with critical CHD, whereas the 20 heterozygous carriers show a spectrum of CVDs (CHD and FTAA, but varying expressivity and incomplete penetrance). Other studies show that knockout of HEY2 in mice results in cardiovascular defects (CVDs), including septal defects, cardiomyopathy, a thin-walled aorta, and valve anomalies. Sources: Literature |
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| Mendeliome v0.6175 | FGF9 | Zornitza Stark Mode of inheritance for gene: FGF9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6174 | OTUD5 |
Zornitza Stark gene: OTUD5 was added gene: OTUD5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: OTUD5 were set to 33131077 Phenotypes for gene: OTUD5 were set to X-linked severe neurodevelopmental delay, hydrocephalus, and early lethality Review for gene: OTUD5 was set to RED Added comment: 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. No functional studies. Sources: Literature |
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| Mendeliome v0.6172 | BCAT2 |
Bryony Thompson gene: BCAT2 was added gene: BCAT2 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: BCAT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BCAT2 were set to 14755340; 25653144 Phenotypes for gene: BCAT2 were set to Hypervalinemia or hyperleucine-isoleucinemia MIM#618850; disorder of branched-chain amino acid metabolism Review for gene: BCAT2 was set to AMBER Added comment: A single case reported with compound heterozygous variants with functional studies demonstrating that the two variants resulted in decreased BCAT2 enzyme activity. Also, a null mouse model has a phenotype similar to human maple syrup urine disease. Sources: NHS GMS |
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| Mendeliome v0.6171 | CLRN2 |
Paul De Fazio gene: CLRN2 was added gene: CLRN2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CLRN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLRN2 were set to 33496845 Phenotypes for gene: CLRN2 were set to Non-syndromic hearing loss Review for gene: CLRN2 was set to AMBER gene: CLRN2 was marked as current diagnostic Added comment: Missense variant segregates with non-syndromic hearing loss in 3 members of a consanguineous family, two from one nuclear family and one from another. The variant was also shown to result in some transcripts being abnormally spliced, resulting in a premature stop codon. Functional studies in zebrafish and mice show the gene plays an essential role in normal organization and maintenance of the auditory hair bundles, and for hearing function. Rated Amber due to supporting functional studies in mice. Sources: Literature |
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| Mendeliome v0.6171 | CFAP47 |
Hazel Phillimore gene: CFAP47 was added gene: CFAP47 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP47 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: CFAP47 were set to PMID: 33472045 Phenotypes for gene: CFAP47 were set to asthenoteratozoospermia; morphological abnormalities of the flagella (MMAF) Review for gene: CFAP47 was set to AMBER Added comment: CFAP47 also known as CXorf22. 3 different missense variants in 3 unrelated Chinese individuals with asthenoteratozoospermia associated with morphological abnormalities of the flagella (MMAF). Immunoblotting and immunofluorescence showed reduced levels of CFAP47 in spermatozoa in all 3 men. A separate asthenoteratozoospermia cohort showed 1 individual with CNV including whole gene deletion of CFAP47. Mouse model (with frameshift variants generated (via CRISPR-Cas9 technology) were sterile and presented with reduced sperm motility and abnormal flagellar morphology. Sources: Literature |
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| Mendeliome v0.6171 | C14orf39 |
Elena Savva gene: C14orf39 was added gene: C14orf39 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C14orf39 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C14orf39 were set to PMID: 33508233; 27796301 Phenotypes for gene: C14orf39 were set to Azoospermia; Premature ovarian insufficiency Review for gene: C14orf39 was set to GREEN Added comment: PMID: 33508233 - 1 family with two males (azoospermia) and 1 female (premature ovarian insufficiency) - 2 unrelated Chinese males with azoospermia All patients had either homozygous PTCs or splice PMID: 27796301 Mouse K/O had azoospermia and ovarian failure Sources: Literature |
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| Mendeliome v0.6167 | ENO1 |
Kristin Rigbye gene: ENO1 was added gene: ENO1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ENO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ENO1 were set to 32488097 Phenotypes for gene: ENO1 were set to Polymicrogyria Review for gene: ENO1 was set to RED Added comment: ENO1 identified as a polymicrogyria candidate gene from the smallest case of 1p36 duplication reported to date, in a 35yo F (onset at 8mo) presenting intellectual disability, microcephaly, epilepsy and perisylvian polymicrogyria. The duplication only encompassed 2 genes, ENO1 and RERE, and gene expression analysis performed using the patient cells revealed reduced expression, mimicking haploinsufficiency. Eno1 inactivation in rats was shown to cause a brain development defect. According to OMIM, ENO1 is deleted in glioblastoma, which is tolerated by the expression of ENO2. Sources: Literature |
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| Mendeliome v0.6166 | METAP1 |
Paul De Fazio gene: METAP1 was added gene: METAP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: METAP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: METAP1 were set to PMID: 32764695 Phenotypes for gene: METAP1 were set to Intellectual disability, aggression, neurodevelopmental delay Review for gene: METAP1 was set to RED gene: METAP1 was marked as current diagnostic Added comment: Biallelic nonsense (NMD-predicted) variant identified in 4 sibs in a consanguineous family with dev delay. One sib had bilateral clinodactyly of her toes and her left 3rd finger, other sibs were not dysmorphic. Rated red due to single consanguineous family. Sources: Literature |
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| Mendeliome v0.6165 | MYADML2 | Zornitza Stark Tag SV/CNV tag was added to gene: MYADML2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6165 | CCDC186 |
Zornitza Stark gene: CCDC186 was added gene: CCDC186 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC186 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC186 were set to 33259146 Phenotypes for gene: CCDC186 were set to Epileptic encephalopathy Review for gene: CCDC186 was set to RED Added comment: One individual reported with bi-allelic truncating variant and EE. Sources: Literature |
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| Mendeliome v0.6164 | KCNN2 |
Ain Roesley gene: KCNN2 was added gene: KCNN2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNN2 were set to 33242881 Phenotypes for gene: KCNN2 were set to neurodevelopmental movement disorders Penetrance for gene: KCNN2 were set to unknown Review for gene: KCNN2 was set to GREEN Added comment: - 11 probands all de novo except for 1 mother-daughter pair. - a mix of null and missense variants - 2/11 with microcephaly, 10/11 motor delay, 7/11 language delay (excluding 2 with regression), all with varying degrees of ID, 3/11 seizures, 7/11 movement disorder, 4/11 cerebellar ataxia, 6/11 MRI anomalies additional variants were noted in 2 patients: 1x cHet for variants in MED12L and 1x de novo TNK2 variant patch clamp functional studies were also done Sources: Literature |
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| Mendeliome v0.6164 | MYADML2 |
Paul De Fazio gene: MYADML2 was added gene: MYADML2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYADML2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYADML2 were set to 32778762 Phenotypes for gene: MYADML2 were set to Cranial asymmetry, reduced bone maturation, multiple dislocations, lumbar lordosis, and prominent clavicles Review for gene: MYADML2 was set to RED gene: MYADML2 was marked as current diagnostic Added comment: 5 sibs from a consanguineous family identified to have biallelic deletion encompassing part of the PYCR1 gene and the coding region of the MYADML2 gene. According to the authors: "All five affected sibs had the most common features of ARCL (autosomal recessive cutis laxa) but not many of the less common ones. We attributed the anomalies not typical for ARCL to MYADML2 deficit, because no other genetic defect possibly a candidate to underlie the skeletal phenotype was found." Phenotype may still be explained by the PYCR1 deletion alone. Sources: Literature |
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| Mendeliome v0.6164 | SQOR |
Zornitza Stark gene: SQOR was added gene: SQOR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SQOR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SQOR were set to 32160317 Phenotypes for gene: SQOR were set to Leigh-like disorder Review for gene: SQOR was set to AMBER Added comment: Two unrelated families and some functional data. Sources: Literature |
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| Mendeliome v0.6162 | HYAL2 |
Zornitza Stark gene: HYAL2 was added gene: HYAL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HYAL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HYAL2 were set to 28081210; 23172227; 26515055 Phenotypes for gene: HYAL2 were set to Cleft lip and palate; cor triatriatum; congenital cardiac malformations Review for gene: HYAL2 was set to AMBER Added comment: 2 unrelated consanguineous extended families (Amish and Arab) with an orofacial clefting phenotype with cardiac anomalies. Sources: Literature |
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| Mendeliome v0.6159 | SLC6A20 | Zornitza Stark Mode of inheritance for gene: SLC6A20 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6156 | SUOX | Zornitza Stark Mode of inheritance for gene: SUOX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6151 | NOS1AP | Zornitza Stark Mode of inheritance for gene: NOS1AP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6147 | DCT |
Zornitza Stark gene: DCT was added gene: DCT was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DCT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DCT were set to 33100333 Phenotypes for gene: DCT were set to Oculocutaneous albinism, type VIII, MIM# 619165 Review for gene: DCT was set to GREEN Added comment: Two unrelated families reported. Functional data including mouse model. Sources: Expert list |
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| Mendeliome v0.6144 | SDHAF1 | Zornitza Stark Mode of inheritance for gene: SDHAF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6141 | NDUFC2 |
Zornitza Stark gene: NDUFC2 was added gene: NDUFC2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NDUFC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFC2 were set to 32969598 Phenotypes for gene: NDUFC2 were set to Mitochondrial complex I deficiency, nuclear type 36, MIM# 619170 Review for gene: NDUFC2 was set to AMBER Added comment: Mitochondrial complex I deficiency nuclear type 36 (MC1DN36) is an autosomal recessive metabolic disorder characterized by global developmental delay, hypotonia, and failure to thrive apparent from infancy or early childhood. Affected individuals usually do not acquire ambulation, show progressive spasticity, and have impaired intellectual development with absent speech. More variable features may include pale optic discs, poor eye contact, seizures, and congenital heart defects. Laboratory studies show increased serum lactate; metabolic acidosis may occur during stress or infection. Brain imaging shows T2-weighted abnormalities in the basal ganglia and brainstem, consistent with a clinical diagnosis of Leigh syndrome. Two unrelated families reported, some functional data. Sources: Expert list |
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| Mendeliome v0.6138 | UPB1 | Zornitza Stark Mode of inheritance for gene: UPB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6135 | UROC1 | Zornitza Stark Mode of inheritance for gene: UROC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6133 | DLX4 |
Zornitza Stark gene: DLX4 was added gene: DLX4 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DLX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DLX4 were set to 25954033; 29738288 Phenotypes for gene: DLX4 were set to Orofacial cleft 15, MIM# 616788 Review for gene: DLX4 was set to RED Added comment: Single family reported and a SNP association study. Sources: Expert list |
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| Mendeliome v0.6132 | DLG1 |
Zornitza Stark gene: DLG1 was added gene: DLG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DLG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DLG1 were set to 28926086 Phenotypes for gene: DLG1 were set to Non-syndromic cleft lip and palate Review for gene: DLG1 was set to RED Added comment: GWAS study PMID: 28926086 found genome-wide significance for several SNPs within this gene, identifying it as a candidate gene for non-syndromic cleft lip with or without cleft palate. Sources: Expert list |
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| Mendeliome v0.6129 | PLEKHA7 | Zornitza Stark Mode of inheritance for gene: PLEKHA7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6125 | GYS2 | Zornitza Stark Mode of inheritance for gene: GYS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6121 | OPA3 | Zornitza Stark Mode of pathogenicity for gene: OPA3 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6120 | OPA3 | Zornitza Stark Mode of inheritance for gene: OPA3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6117 | FOXF1 | Zornitza Stark Mode of inheritance for gene: FOXF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6114 | STEAP3 | Zornitza Stark Mode of inheritance for gene: STEAP3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6112 | FTH1 |
Zornitza Stark gene: FTH1 was added gene: FTH1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FTH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FTH1 were set to 11389486 Phenotypes for gene: FTH1 were set to Hemochromatosis, type 5, MIM# 615517 Review for gene: FTH1 was set to RED Added comment: One multi-generational family with 5' UTR variant. Sources: Expert list |
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| Mendeliome v0.6111 | CYBRD1 |
Zornitza Stark gene: CYBRD1 was added gene: CYBRD1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CYBRD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CYBRD1 were set to 15338274 Phenotypes for gene: CYBRD1 were set to Iron overload Review for gene: CYBRD1 was set to RED Added comment: Paucity of publications. One of the variants reported in PMID 15338274, p.Arg226His is present in over 1,000 hets in gnomad. Sources: Expert list |
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| Mendeliome v0.6109 | BMP6 |
Zornitza Stark gene: BMP6 was added gene: BMP6 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: BMP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BMP6 were set to 26582087; 32464486 Phenotypes for gene: BMP6 were set to Iron overload, mild to moderate Review for gene: BMP6 was set to GREEN Added comment: More than 9 individuals reported with iron overload and variants in this gene. Sources: Expert list |
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| Mendeliome v0.6107 | CREB3L3 |
Bryony Thompson gene: CREB3L3 was added gene: CREB3L3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CREB3L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694 Phenotypes for gene: CREB3L3 were set to Hyperlipidaemia; hypertriglyceridemia Review for gene: CREB3L3 was set to AMBER Added comment: PMID: 26427795 - a loss of function variant (c.359delG p.K120fsX20) was identified in 2 affected adult siblings and a 13 yo normotriglyceridemic daughter of one of the siblings. PMID: 21666694 - Lipoprotein profiles of the families of 4 individuals with CREB3L3 nonsense mutations showed a significantly elevated mean plasma TG level in 11 mutation carriers compared with 5 non-carrier first-degree relatives (9.67 ± 4.70 vs. 1.66 ± 0.55 mM, P = 0.021, Wilcoxon test). 3 of those families have the same variant - Lys245GlufsTer130, which has 126 (281,946 alleles) hets in gnomAD v2.1. PMID: 32580631 - case-control analysis of nonmonogenic severe hypertriglyceridemia cases (N=265) vs normolipidemic controls (N=477), identified 5 cases with LoF variants (3 of whom had the Lys245GlufsTer130 frameshift) and none in controls. OR 20.2 (95% CI 1.11–366.1) p = 0.002, adjusted p = 0.03. The frequency of Lys245GlufsTer130 is higher than expected for a dominant disorder, but other loss of function variants have been identified. The gene may be associated with variable penetrance. There are multiple supporting null mouse models with hyperlipidaemia. Sources: Expert list |
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| Mendeliome v0.6105 | GPIHBP1 |
Bryony Thompson gene: GPIHBP1 was added gene: GPIHBP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GPIHBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GPIHBP1 were set to 17883852; 19304573; 20026666; 17403372 Phenotypes for gene: GPIHBP1 were set to Hyperlipoproteinemia, type 1D MIM#615947; familial chylomicronemia syndrome Review for gene: GPIHBP1 was set to GREEN gene: GPIHBP1 was marked as current diagnostic Added comment: Well-established cause of familial chylomicronemia (see OMIM). Greater than 3 families reported and a supporting mouse model. Sources: Expert list |
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| Mendeliome v0.6102 | CBY1 |
Bryony Thompson gene: CBY1 was added gene: CBY1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CBY1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CBY1 were set to 33131181; 25103236; 25220153 Phenotypes for gene: CBY1 were set to intellectual disability; cerebellar ataxia; molar tooth sign; polydactyly; Joubert syndrome Review for gene: CBY1 was set to GREEN Added comment: Three cases in two unrelated consanguineous families with homozygous loss of function variants. Multiple null model organisms recapitulate the human phenotype: Null mouse model had cystic kidneys, a phenotype common to ciliopathies. Reducing Cby levels in Xenopus laevis model reduced the density of multiciliated cells, the number of basal bodies per multiciliated cell, and the numbers of neural tube primary cilia; it also led to abnormal development of the neural crest, central nervous system, and pronephros. Depletion of cby1 in zebrafish results in ciliopathy‐related phenotypes. Sources: Literature |
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| Mendeliome v0.6100 | ZMYND15 |
Bryony Thompson gene: ZMYND15 was added gene: ZMYND15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZMYND15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZMYND15 were set to 24431330; 33169450; 20675388 Phenotypes for gene: ZMYND15 were set to Severe oligozoospermia Review for gene: ZMYND15 was set to GREEN Added comment: 4 unrelated consanguineous cases with homozygous loss of function variants. Zmynd15-null male mice display reduced testis weight and azoospermia Sources: Literature |
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| Mendeliome v0.6097 | PNPLA1 | Zornitza Stark Mode of inheritance for gene: PNPLA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6095 | TMEM251 |
Bryony Thompson gene: TMEM251 was added gene: TMEM251 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM251 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM251 were set to 33252156 Phenotypes for gene: TMEM251 were set to Dysostosis multiplex‐like skeletal dysplasia; severe short stature Review for gene: TMEM251 was set to AMBER Added comment: Two unrelated consanguineous families with homozygous variants (c.133C>T; p.Arg45Trp and c.215dupA; p.Tyr72Ter), with co-segregation data in one family. Preliminary in vitro functional assays conducted - Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes. Sources: Literature |
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| Mendeliome v0.6092 | LOR | Zornitza Stark Mode of inheritance for gene: LOR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6089 | CYP4F22 | Zornitza Stark Mode of inheritance for gene: CYP4F22 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6086 | CERS3 | Zornitza Stark Mode of inheritance for gene: CERS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6083 | ALOX12B | Zornitza Stark Mode of inheritance for gene: ALOX12B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6080 | ALX3 | Zornitza Stark Mode of inheritance for gene: ALX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6077 | ALX1 | Zornitza Stark Mode of inheritance for gene: ALX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6074 | HIST1H1E | Zornitza Stark Mode of inheritance for gene: HIST1H1E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6071 | EED | Zornitza Stark Mode of inheritance for gene: EED was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6068 | CLCN1 | Zornitza Stark Mode of inheritance for gene: CLCN1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6065 | TUBG1 | Zornitza Stark Mode of inheritance for gene: TUBG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6062 | TUBB3 | Zornitza Stark Mode of inheritance for gene: TUBB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6059 | TUBB2B | Zornitza Stark Mode of inheritance for gene: TUBB2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6056 | TUBB | Zornitza Stark Mode of inheritance for gene: TUBB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6053 | FZD4 | Zornitza Stark Mode of inheritance for gene: FZD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6050 | TSPAN12 | Zornitza Stark Mode of inheritance for gene: TSPAN12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6047 | PPP2R5D | Zornitza Stark Mode of pathogenicity for gene: PPP2R5D was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6046 | PPP2R5D | Zornitza Stark Mode of inheritance for gene: PPP2R5D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6043 | KAT6B | Zornitza Stark Mode of pathogenicity for gene: KAT6B was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6042 | KAT6B | Zornitza Stark Mode of inheritance for gene: KAT6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6039 | DVL1 | Zornitza Stark Mode of pathogenicity for gene: DVL1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6038 | DVL1 | Zornitza Stark Mode of inheritance for gene: DVL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6035 | SCAMP5 | Zornitza Stark edited their review of gene: SCAMP5: Added comment: PMID 33390987: Four unrelated individuals reported with same de novo missense variant, p. Gly180Trp. The onset age of seizures was ranged from 6 to 15 months. Patients had different types of seizures, including focal seizures, generalized tonic-clonic seizures and tonic seizure. One patient showed typical autism spectrum disorder (ASD) symptoms. Electroencephalogram (EEG) findings presented as focal or multifocal discharges, sometimes spreading to generalization. Brain magnetic resonance imaging (MRI) abnormalities were present in each patient. Severe intellectual disability and language and motor developmental disorders were found in our patients, with all patients having poor language development and were nonverbal at last follow-up. All but one of the patients could walk independently in childhood, but the ability to walk independently in one patient had deteriorated with age. All patients had abnormal neurological exam findings, mostly signs of extrapyramidal system involvement. Dysmorphic features were found in 2/4 patients, mainly in the face and trunk.; Changed publications: 31439720, 33390987 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6030 | ZNF526 | Zornitza Stark Mode of inheritance for gene: ZNF526 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6023 | BCS1L | Zornitza Stark Mode of inheritance for gene: BCS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6020 | MRPS22 | Zornitza Stark Mode of inheritance for gene: MRPS22 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6018 | CELF2 |
Zornitza Stark gene: CELF2 was added gene: CELF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CELF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CELF2 were set to 33131106 Phenotypes for gene: CELF2 were set to Developmental and epileptic encephalopathy Review for gene: CELF2 was set to GREEN Added comment: Five unrelated individuals reported. Four with de novo variants, and one inherited from a mosaic mother. Notably, all identified variants, except for c.272‐1G>C, were clustered within 20 amino acid residues of the C‐terminus, which might be a nuclear localization signal. Sources: Literature |
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| Mendeliome v0.6016 | FGF13 |
Zornitza Stark gene: FGF13 was added gene: FGF13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FGF13 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: FGF13 were set to 33245860 Phenotypes for gene: FGF13 were set to Intellectual disability; epilepsy Mode of pathogenicity for gene: FGF13 was set to Other Review for gene: FGF13 was set to GREEN Added comment: Two sibling pairs and three unrelated males reported who presented in infancy with intractable focal seizures and severe developmental delay. The variants were located in the N-terminal domain of the A isoform of FGF13/FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Sources: Literature |
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| Mendeliome v0.6014 | SCUBE3 |
Zornitza Stark gene: SCUBE3 was added gene: SCUBE3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SCUBE3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCUBE3 were set to 33308444 Phenotypes for gene: SCUBE3 were set to Short stature; skeletal abnormalities; craniofacial abnormalities; dental anomalies Review for gene: SCUBE3 was set to GREEN Added comment: Eighteen affected individuals from nine unrelated families reported with a consistent phenotype characterised by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. Sources: Literature |
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| Mendeliome v0.6012 | UBR7 |
Zornitza Stark gene: UBR7 was added gene: UBR7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBR7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UBR7 were set to 33340455 Phenotypes for gene: UBR7 were set to Intellectual disability; epilepsy; hypothyroidism; congenital anomalies; dysmorphic features Review for gene: UBR7 was set to GREEN Added comment: Seven individuals from 6 unrelated families. All had developmental delay, and all males had urogenital anomalies, namely cryptorchidism in 5/6 and small penis in 1/6. Six individuals had seizures and hypotonia. Hypothyroidism was present in 4/7 individuals, and ptosis was noted in 6/7 individuals. Five individuals exhibited cardiac abnormalities: two had ventricular septal defect, one had atrial septal defect, one had a patent ductus arteriosus requiring surgery, and the other had a patent ductus arteriosus and a patent foramen ovale that both closed spontaneously. Five individuals had short stature (height < 3rd percentile). Physical examination revealed various dysmorphic features, including prominent forehead (3/7), hypertelorism (4/7), telecanthus (1/7), epicanthus(1/7), downslanting palpebral fissures (3/7), thick eyebrow (1/7), low-set ears (3/7), long philtrum (2/7), unilateral single transverse palmar crease (1/7), and hypertrichosis (1/7). Sources: Literature |
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| Mendeliome v0.6008 | RABL2A | Zornitza Stark Mode of inheritance for gene: RABL2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6003 | CEP250 | Zornitza Stark Mode of inheritance for gene: CEP250 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6002 | RABL2A |
Eleanor Williams gene: RABL2A was added gene: RABL2A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RABL2A was set to Unknown Publications for gene: RABL2A were set to 33075816 Phenotypes for gene: RABL2A were set to male infertility; ciliopathy Review for gene: RABL2A was set to RED Added comment: PMID: 33075816 - Ding et al 2020 - with the aim of identifying variants that affect male fertility, the authors report on mice expressing two RABL2A SNPs found to be rare (MAF between 2% and 0.02% in gnomAD, with a deleterious prediction from SIFT and PolyPhen-2, and to affect protein stability. Mice homozygous for these variants (p.L119F and p.V158F) were found to be show ciliopathy-associated disorders including male infertility, early growth retardation, excessive weight gain in adulthood, heterotaxia, pre-axial polydactyly, neural tube defects and hydrocephalus. Sources: Literature |
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| Mendeliome v0.6000 | VCAN | Zornitza Stark Mode of inheritance for gene: VCAN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5997 | CAPN5 | Zornitza Stark Mode of inheritance for gene: CAPN5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5994 | UBIAD1 | Zornitza Stark Mode of inheritance for gene: UBIAD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5991 | TGFBI | Zornitza Stark Mode of inheritance for gene: TGFBI was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5988 | TACSTD2 | Zornitza Stark Mode of inheritance for gene: TACSTD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5984 | ZEB1 | Zornitza Stark Mode of inheritance for gene: ZEB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5981 | ZNF469 | Zornitza Stark Mode of inheritance for gene: ZNF469 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5978 | PIKFYVE | Zornitza Stark Mode of inheritance for gene: PIKFYVE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5975 | OVOL2 | Zornitza Stark Tag 5'UTR tag was added to gene: OVOL2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5975 | OVOL2 | Zornitza Stark Mode of inheritance for gene: OVOL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5972 | KRT3 | Zornitza Stark Mode of inheritance for gene: KRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5969 | DCN | Zornitza Stark Mode of inheritance for gene: DCN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5966 | COL8A2 | Zornitza Stark Mode of inheritance for gene: COL8A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5963 | STX3 | Zornitza Stark Mode of inheritance for gene: STX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5960 | SPINT2 | Zornitza Stark Mode of inheritance for gene: SPINT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5957 | SLC9A3 | Zornitza Stark Mode of inheritance for gene: SLC9A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5954 | SLC5A1 | Zornitza Stark Mode of inheritance for gene: SLC5A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5951 | SLC39A4 | Zornitza Stark Mode of inheritance for gene: SLC39A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5948 | SLC26A3 | Zornitza Stark Mode of inheritance for gene: SLC26A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5947 | SLC51B |
Zornitza Stark gene: SLC51B was added gene: SLC51B was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SLC51B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC51B were set to 28898457 Phenotypes for gene: SLC51B were set to Congenital diarrhoea; Cholestasis Review for gene: SLC51B was set to RED Added comment: Two siblings reported with homozygous LOF variant in this gene and congenital diarrhoea/cholestasis. Sources: Expert Review |
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| Mendeliome v0.5944 | SLC10A2 | Zornitza Stark Mode of inheritance for gene: SLC10A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5940 | PLVAP | Zornitza Stark Mode of inheritance for gene: PLVAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5937 | NEUROG3 | Zornitza Stark Mode of inheritance for gene: NEUROG3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5934 | TMPRSS15 | Zornitza Stark Mode of inheritance for gene: TMPRSS15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5931 | TTC37 | Zornitza Stark Mode of inheritance for gene: TTC37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5928 | WNT2B | Zornitza Stark Mode of inheritance for gene: WNT2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5925 | MYO5B | Zornitza Stark Mode of inheritance for gene: MYO5B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5923 | LCT | Zornitza Stark Mode of inheritance for gene: LCT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5920 | CAMK2B | Zornitza Stark Mode of inheritance for gene: CAMK2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5917 | RALGAPB |
Elena Savva gene: RALGAPB was added gene: RALGAPB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RALGAPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RALGAPB were set to PMID: 32853829 Phenotypes for gene: RALGAPB were set to Neurodevelopmental disorders, autism Review for gene: RALGAPB was set to GREEN Added comment: PMID: 32853829 - 2 patients with de novo missense variants, 1 patient with a de novo PTC with autism spectrum disorder from a large cohort. Reviews previous publications and identifies 10 de novo variants (5 PTCs, 5 missense) in patients with ASD (7/10), epilepsy (2/10) and developmental delay (1/10). Functional studies of patient cells show reduced mRNA expression (PTC). Sources: Literature |
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| Mendeliome v0.5914 | RNU7-1 |
Ee Ming Wong gene: RNU7-1 was added gene: RNU7-1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU7-1 were set to PMID: 33230297 Phenotypes for gene: RNU7-1 were set to PMID: 33230297 Review for gene: RNU7-1 was set to GREEN gene: RNU7-1 was marked as current diagnostic Added comment: - 16 affected individuals from 11 families - - Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of replication-dependent histone (RDH) mRNAs Sources: Literature |
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| Mendeliome v0.5914 | RPL3L |
Elena Savva gene: RPL3L was added gene: RPL3L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RPL3L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RPL3L were set to PMID: 32514796; 32870709 Phenotypes for gene: RPL3L were set to Neonatal dilated cardiomyopathy Review for gene: RPL3L was set to GREEN Added comment: PMID: 32514796 - 5 hom/chet individuals from three independent families who presented with severe neonatal dilated cardiomyopathy. Unaffected sibs were either carriers of a single variant or homozygous wildtype. PMID: 32870709 - 1 hom patient w/ neonatal DCM Sources: Literature |
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| Mendeliome v0.5914 | LSM11 |
Ee Ming Wong gene: LSM11 was added gene: LSM11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LSM11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSM11 were set to PMID: 33230297 Phenotypes for gene: LSM11 were set to type I interferonopathy Aicardi–Goutières syndrome Review for gene: LSM11 was set to AMBER gene: LSM11 was marked as current diagnostic Added comment: - Two affected siblings from a consanguineous family carrying a homozygous variant in LSM11 - Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of replication-dependent histone (RDH) mRNAs - Knockdown of LSM11 in THP-1 cells results in an increase in misprocessed RDH mRNA and interferon signaling Sources: Literature |
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| Mendeliome v0.5914 | DPH2 |
Paul De Fazio changed review comment from: One family reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency. Another family was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative. In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952. Sources: Literature; to: One 19 month old reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency (gross motor delay, not walking, fine motor and expressive language delays, macrocephaly) Another family (sibs) was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative. Patients had ID and microcephaly (in contrast to the 19 month old above). In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952. Sources: Literature |
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| Mendeliome v0.5914 | DPH2 |
Paul De Fazio gene: DPH2 was added gene: DPH2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DPH2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPH2 were set to 32576952; 27421267 Phenotypes for gene: DPH2 were set to Diphthamide-deficiency syndrome Review for gene: DPH2 was set to AMBER gene: DPH2 was marked as current diagnostic Added comment: One family reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency. Another family was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative. In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952. Sources: Literature |
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| Mendeliome v0.5914 | FBRSL1 |
Elena Savva gene: FBRSL1 was added gene: FBRSL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FBRSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FBRSL1 were set to PMID: 32424618 Phenotypes for gene: FBRSL1 were set to Malformation and intellectual disability syndrome Review for gene: FBRSL1 was set to GREEN Added comment: Three children with de novo PTCs that escape NMD, and an overlapping syndromic phenotype with respiratory insufficiency, postnatal growth restriction, microcephaly, global developmental delay and other malformations. 2/3 had heart defects, cleft palate and hearing impairement. Supported by Xenopus oocyte functional studies Sources: Literature |
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| Mendeliome v0.5912 | EPCAM | Zornitza Stark Mode of inheritance for gene: EPCAM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5909 | DGAT1 | Zornitza Stark Mode of inheritance for gene: DGAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5906 | CPA6 | Zornitza Stark Mode of inheritance for gene: CPA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5904 | CPA6 |
Zornitza Stark edited their review of gene: CPA6: Added comment: Homozygous p.A270V variant reported in four siblings with Febrile seizures, familial, 11 (MIM 614418)(PMID:21922598), some functional data. Present in gnomad as hets but no homs. Also note one of the heterozygous individuals initially reported was subsequently found to have a second missense variant, PMID 23105115. Disputed association between mono allelic variants and disease: variants reported have high frequency in gnomad, not in keeping with Mendelian disorder.; Changed rating: AMBER; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal |
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| Mendeliome v0.5903 | HSD17B10 | Zornitza Stark Mode of inheritance for gene: HSD17B10 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5900 | HMGCS2 | Zornitza Stark Mode of inheritance for gene: HMGCS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5899 | HMGCL | Zornitza Stark Tag SV/CNV tag was added to gene: HMGCL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5897 | HMGCL | Zornitza Stark Mode of inheritance for gene: HMGCL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5894 | GLUD1 | Zornitza Stark Mode of inheritance for gene: GLUD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5891 | AGPAT2 | Zornitza Stark Tag SV/CNV tag was added to gene: AGPAT2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5889 | AGPAT2 | Zornitza Stark Mode of inheritance for gene: AGPAT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5886 | LPIN1 | Zornitza Stark Mode of inheritance for gene: LPIN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5883 | MLYCD | Zornitza Stark Mode of inheritance for gene: MLYCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5880 | SLC25A20 | Zornitza Stark Mode of inheritance for gene: SLC25A20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5877 | GABRD | Zornitza Stark Mode of inheritance for gene: GABRD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5873 | SPR | Zornitza Stark Mode of inheritance for gene: SPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5870 | PRRT2 | Zornitza Stark Mode of inheritance for gene: PRRT2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5867 | KCNQ3 | Zornitza Stark Mode of inheritance for gene: KCNQ3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5862 | SCARF2 | Zornitza Stark Mode of inheritance for gene: SCARF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5857 | NAA10 | Zornitza Stark Tag 5'UTR tag was added to gene: NAA10. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5855 | PRR12 | Zornitza Stark Mode of inheritance for gene: PRR12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5852 | PRSS56 | Zornitza Stark Mode of inheritance for gene: PRSS56 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5849 | GJA8 | Zornitza Stark Mode of inheritance for gene: GJA8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5846 | ATIC | Zornitza Stark Mode of inheritance for gene: ATIC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5844 | FZD5 |
Zornitza Stark gene: FZD5 was added gene: FZD5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FZD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FZD5 were set to 32737437; 26908622 Phenotypes for gene: FZD5 were set to Coloboma Review for gene: FZD5 was set to GREEN Added comment: Four unrelated families reported. Sources: Literature |
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| Mendeliome v0.5841 | STRA6 | Zornitza Stark Mode of inheritance for gene: STRA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5838 | SOX2 | Zornitza Stark Mode of inheritance for gene: SOX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5835 | SIX6 | Zornitza Stark Mode of inheritance for gene: SIX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5832 | RERE | Zornitza Stark Mode of inheritance for gene: RERE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5827 | RAX | Zornitza Stark Mode of inheritance for gene: RAX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5824 | RARB | Zornitza Stark Mode of pathogenicity for gene: RARB was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5823 | RARB | Zornitza Stark Mode of inheritance for gene: RARB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5820 | RARA | Zornitza Stark Mode of inheritance for gene: RARA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5817 | PXDN | Zornitza Stark Mode of inheritance for gene: PXDN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5814 | SMOC1 | Zornitza Stark Mode of inheritance for gene: SMOC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5811 | MFRP | Zornitza Stark Mode of inheritance for gene: MFRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5808 | MAB21L2 | Zornitza Stark Mode of inheritance for gene: MAB21L2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5805 | PDSS1 | Zornitza Stark Mode of inheritance for gene: PDSS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5801 | POLR1A | Zornitza Stark Mode of inheritance for gene: POLR1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5799 | LOXL3 |
Zornitza Stark gene: LOXL3 was added gene: LOXL3 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: LOXL3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LOXL3 were set to 30362103; 25663169 Phenotypes for gene: LOXL3 were set to Stickler syndrome Review for gene: LOXL3 was set to AMBER Added comment: Two unrelated families reported with homozygous missense variants, mouse model supports gene-disease association. Sources: Expert Review |
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| Mendeliome v0.5796 | RBP4 | Zornitza Stark Mode of inheritance for gene: RBP4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5793 | VAX1 | Zornitza Stark Mode of inheritance for gene: VAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5789 | VSX2 | Zornitza Stark Mode of inheritance for gene: VSX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5786 | WDR37 | Zornitza Stark Mode of inheritance for gene: WDR37 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5783 | ALDH1A3 | Zornitza Stark Mode of inheritance for gene: ALDH1A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5779 | VEGFC | Zornitza Stark Mode of inheritance for gene: VEGFC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5773 | RNASEH2B | Zornitza Stark Mode of inheritance for gene: RNASEH2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5770 | PDGFB | Zornitza Stark Mode of inheritance for gene: PDGFB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5769 | XYLT1 |
Zornitza Stark Tag SV/CNV tag was added to gene: XYLT1. Tag STR tag was added to gene: XYLT1. |
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| Mendeliome v0.5769 | TUSC3 | Zornitza Stark Tag SV/CNV tag was added to gene: TUSC3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5767 | TUSC3 | Zornitza Stark Mode of inheritance for gene: TUSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5766 | TMEM5 | Zornitza Stark Tag new gene name tag was added to gene: TMEM5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5764 | TMEM165 | Zornitza Stark Mode of inheritance for gene: TMEM165 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5759 | SLC35C1 | Zornitza Stark Mode of inheritance for gene: SLC35C1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5754 | GNE | Zornitza Stark Mode of inheritance for gene: GNE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5753 | EXT2 | Zornitza Stark Mode of inheritance for gene: EXT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5749 | CHSY1 | Zornitza Stark Mode of inheritance for gene: CHSY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5746 | DHDDS | Zornitza Stark Mode of inheritance for gene: DHDDS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5745 | DHDDS | Zornitza Stark Tag founder tag was added to gene: DHDDS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5744 | FBLN1 | Zornitza Stark Mode of inheritance for gene: FBLN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5741 | FBLN1 | Zornitza Stark Mode of inheritance for gene: FBLN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5739 | TBL1X |
Elena Savva gene: TBL1X was added gene: TBL1X was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TBL1X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: TBL1X were set to PMID: 27603907 Phenotypes for gene: TBL1X were set to Hypothyroidism, congenital, nongoitrous, 8 MIM#301033 Review for gene: TBL1X was set to GREEN Added comment: PMID: 27603907 - mostly males but also a female diagnosed with central hypothyroidism. 6 families reported (5/6 missense, 1/6 splice). Supported by functional studies ->LOF All mutations were located in the highly conserved WD40-repeat domains. Sources: Literature |
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| Mendeliome v0.5739 | ST3GAL5 | Zornitza Stark Tag founder tag was added to gene: ST3GAL5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5737 | ST3GAL5 | Zornitza Stark Mode of inheritance for gene: ST3GAL5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5734 | SUCLA2 | Zornitza Stark Mode of inheritance for gene: SUCLA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5731 | RFT1 | Zornitza Stark Mode of inheritance for gene: RFT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5728 | CHST6 | Zornitza Stark Mode of inheritance for gene: CHST6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5725 | MGAT2 | Zornitza Stark Mode of inheritance for gene: MGAT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5722 | MPI | Zornitza Stark Mode of inheritance for gene: MPI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5719 | PGM3 | Zornitza Stark Mode of inheritance for gene: PGM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5716 | PGAP3 | Zornitza Stark Mode of inheritance for gene: PGAP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5713 | PGAP2 | Zornitza Stark Mode of inheritance for gene: PGAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5710 | PIGV | Zornitza Stark Mode of inheritance for gene: PIGV was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5706 | PIGO | Zornitza Stark Mode of inheritance for gene: PIGO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5705 | PIGN |
Zornitza Stark Tag SV/CNV tag was added to gene: PIGN. Tag founder tag was added to gene: PIGN. |
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| Mendeliome v0.5703 | PIGN | Zornitza Stark Mode of inheritance for gene: PIGN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5700 | PIGA | Zornitza Stark Mode of inheritance for gene: PIGA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5699 | PIGL |
Zornitza Stark Tag SV/CNV tag was added to gene: PIGL. Tag founder tag was added to gene: PIGL. |
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| Mendeliome v0.5697 | PIGL | Zornitza Stark Mode of inheritance for gene: PIGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5694 | B3GALT6 | Zornitza Stark Mode of inheritance for gene: B3GALT6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5691 | B3GALNT2 | Zornitza Stark Mode of inheritance for gene: B3GALNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5688 | MPDU1 | Zornitza Stark Mode of inheritance for gene: MPDU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5685 | DPAGT1 | Zornitza Stark Mode of inheritance for gene: DPAGT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5682 | DOLK | Zornitza Stark Mode of inheritance for gene: DOLK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5679 | SLC2A1 | Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5675 | ERCC1 | Zornitza Stark Mode of inheritance for gene: ERCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5672 | POR | Zornitza Stark Mode of inheritance for gene: POR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5669 | MYH6 | Zornitza Stark Mode of inheritance for gene: MYH6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5666 | EZH2 | Zornitza Stark Mode of inheritance for gene: EZH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5663 | COG6 | Zornitza Stark Mode of inheritance for gene: COG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5660 | COG5 | Zornitza Stark Mode of inheritance for gene: COG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5657 | FIGLA | Zornitza Stark Mode of inheritance for gene: FIGLA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5654 | ESR1 | Zornitza Stark Mode of inheritance for gene: ESR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5650 | BMP15 | Zornitza Stark Mode of inheritance for gene: BMP15 was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5648 | PANX1 |
Zornitza Stark gene: PANX1 was added gene: PANX1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PANX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PANX1 were set to 30918116; 32838805 Phenotypes for gene: PANX1 were set to Oocyte maturation defect 7, MIM# 618550 Review for gene: PANX1 was set to AMBER Added comment: Two unrelated families, some functional data. Clinical presentation is with infertility. Sources: Expert list |
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| Mendeliome v0.5646 | NANOS3 |
Bryony Thompson gene: NANOS3 was added gene: NANOS3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NANOS3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NANOS3 were set to 25054146; 24091668 Phenotypes for gene: NANOS3 were set to Primary ovarian insufficiency Review for gene: NANOS3 was set to AMBER Added comment: A homozygous missense (p.Glu120Lys) was identified in two Brazillian sisters with primary amenorrhea, and supporting in vitro functional assays. A heterozygous missense (p.Arg153Trp) was identified in a Chinese woman with POI, with supporting in vitro functional assays. Also, supporting null mouse model. Sources: Literature |
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| Mendeliome v0.5644 | MSH5 |
Bryony Thompson gene: MSH5 was added gene: MSH5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MSH5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MSH5 were set to 28175301; 9916805; 24970489 Phenotypes for gene: MSH5 were set to Premature ovarian failure 13 MIM#617442 Review for gene: MSH5 was set to AMBER Added comment: A homozygous missense mutation (p.D487Y) in two sisters with POI. Also, homologous mutation in mice results in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. Null mouse model is viable, but sterile. A case with congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome had a de novo t(6;14)(p21;q32) translocation, including CYP21A2,TNXB and MSH5. Sources: Literature |
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| Mendeliome v0.5642 | PATL2 |
Zornitza Stark gene: PATL2 was added gene: PATL2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PATL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PATL2 were set to 28965844; 28965849; 32048119; 30765866 Phenotypes for gene: PATL2 were set to Oocyte maturation defect 4, MIM# 617743 Review for gene: PATL2 was set to GREEN Added comment: More than 5 unrelated families reported, presentation is with infertility. Sources: Expert list |
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| Mendeliome v0.5638 | PGRMC1 |
Zornitza Stark gene: PGRMC1 was added gene: PGRMC1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PGRMC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PGRMC1 were set to 25246111; 18782852 Phenotypes for gene: PGRMC1 were set to Premature ovarian failure Review for gene: PGRMC1 was set to RED Added comment: One family with translocation reported and two affected individuals. Another individual identified as part of a cohort with a missense variant (H165R), but the variant is present in >200 hets in gnomad. Subsequent cohort study did not find an association. Sources: Expert list |
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| Mendeliome v0.5636 | EIF4ENIF1 |
Bryony Thompson gene: EIF4ENIF1 was added gene: EIF4ENIF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF4ENIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF4ENIF1 were set to 31810472; 23902945; 33095795 Phenotypes for gene: EIF4ENIF1 were set to Primary ovarian insufficiency Review for gene: EIF4ENIF1 was set to AMBER Added comment: 3 families: A missense (p.Q842P) segregated between a mother and daughter with diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI). A nonsense variant (p.Ser429Ter) segregated in 7 affected women over 3 consecutive generations with early menopause at approximately age 30 years. A missense (p.Lys669Arg) was identified in a Brazilian case with POI. Sources: Literature |
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| Mendeliome v0.5633 | POF1B | Zornitza Stark Mode of inheritance for gene: POF1B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5630 | POU5F1 |
Zornitza Stark gene: POU5F1 was added gene: POU5F1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: POU5F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU5F1 were set to 21273125 Phenotypes for gene: POU5F1 were set to Premature ovarian failure Review for gene: POU5F1 was set to RED Added comment: Single individual reported in 2011 and a missense variant. Sources: Expert list |
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| Mendeliome v0.5628 | CCDC141 |
Bryony Thompson gene: CCDC141 was added gene: CCDC141 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC141 was set to Unknown Publications for gene: CCDC141 were set to 27014940; 28324054; 25192046 Phenotypes for gene: CCDC141 were set to Anosmic hypogonadotropic hypogonadism Review for gene: CCDC141 was set to AMBER Added comment: A consanguineous family had a homozygous nonsense variant, but also had a homozygous missense in FEZF1. 3 other families reported with heterozygous variants, but other variants in other genes present. In an olfactory mouse model, Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration. Sources: Literature |
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| Mendeliome v0.5627 | SGO2 |
Zornitza Stark gene: SGO2 was added gene: SGO2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SGO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SGO2 were set to 27629923 Phenotypes for gene: SGO2 were set to Perrault syndrome Review for gene: SGO2 was set to RED Added comment: Single affected individual reported, though deafness was thought to be explained by a CLDN14 variant. Protein is known to be involved in meiosis. Sources: Expert list |
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| Mendeliome v0.5626 | SOHLH2 |
Zornitza Stark gene: SOHLH2 was added gene: SOHLH2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SOHLH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SOHLH2 were set to 24524832; 19014927 Phenotypes for gene: SOHLH2 were set to Premature ovarian failure Review for gene: SOHLH2 was set to RED Added comment: Heterozygous variants in this gene found to be enriched in a cohort of women with POF, substantial data including mouse models implicating this gene in infertility but paucity of well characterised cases. Sources: Expert list |
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| Mendeliome v0.5624 | SYCE1 |
Zornitza Stark gene: SYCE1 was added gene: SYCE1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SYCE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SYCE1 were set to 25062452; 32917591; 32741963; 32402064; 31925770; 31916078 Phenotypes for gene: SYCE1 were set to Premature ovarian failure 12, MIM# 616947; Spermatogenic failure 15 ,MIM#616950 Review for gene: SYCE1 was set to GREEN Added comment: More than 5 families reported with POF/SF and bi-allelic variants in this gene. Mechanism is thought to be disruption of meiosis, mouse model data also supports gene-disease association. Sources: Expert list |
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| Mendeliome v0.5623 | DACH2 |
Zornitza Stark gene: DACH2 was added gene: DACH2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DACH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DACH2 were set to 15459172 Phenotypes for gene: DACH2 were set to Primary ovarian insufficiency Review for gene: DACH2 was set to RED Added comment: In a small candidate gene study, missense were more common in POI cases than controls (p= 0.0125). 5 missense reported in 7 POI cases, although 2 of the missense are too common in gnomAD for a dominant disorder. No other reports with evidence for an association with POI. Sources: Expert list |
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| Mendeliome v0.5620 | TUBB8 | Zornitza Stark Mode of inheritance for gene: TUBB8 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5617 | WEE2 | Zornitza Stark Mode of inheritance for gene: WEE2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5615 | ZP1 |
Zornitza Stark gene: ZP1 was added gene: ZP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ZP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ZP1 were set to 24670168; 30810869; 32573113; 33272616 Phenotypes for gene: ZP1 were set to Oocyte maturation defect 1, MIM# 615774 Review for gene: ZP1 was set to GREEN Added comment: Multiple unrelated individuals reported, presents as primary infertility. Sources: Expert list |
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| Mendeliome v0.5612 | ZP3 |
Zornitza Stark gene: ZP3 was added gene: ZP3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ZP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZP3 were set to 28886344; 30810869; 33272616; 32573113 Phenotypes for gene: ZP3 were set to Oocyte maturation defect 3, MIM# 617712 Review for gene: ZP3 was set to GREEN Added comment: Oocyte maturation defect with normal ovarian reserves and menstrual cycles, presents as infertility. Sources: Expert list |
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| Mendeliome v0.5609 | CDC40 |
Zornitza Stark gene: CDC40 was added gene: CDC40 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDC40 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CDC40 were set to 33220177 Phenotypes for gene: CDC40 were set to Pontocerebellar hypoplasia; microcephaly; seizures Review for gene: CDC40 was set to RED Added comment: Single individual reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID, thrombocytopaenia, anaemia. Interaction with PPIL1 and mouse model support gene-disease association. Gene referred to as PRP17 in paper. Sources: Literature |
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| Mendeliome v0.5607 | PPIL1 |
Zornitza Stark gene: PPIL1 was added gene: PPIL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPIL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPIL1 were set to 33220177 Phenotypes for gene: PPIL1 were set to Pontocerebellar hypoplasia; microcephaly; seizures Review for gene: PPIL1 was set to GREEN Added comment: 17 individuals from 9 unrelated families reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID. Mouse models support gene-disease association. Sources: Literature |
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| Mendeliome v0.5605 | FRA12A |
Bryony Thompson STR: FRA12A was added STR: FRA12A was added to Mendeliome. Sources: Other 5'UTR tags were added to STR: FRA12A. Mode of inheritance for STR: FRA12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: FRA12A were set to 17236128 Phenotypes for STR: FRA12A were set to Mental retardation, FRA12A type MIM#136630 Review for STR: FRA12A was set to AMBER Added comment: NM_173602.2:c.-137CGG[X] All individuals expressing FRA12A had CGG-repeat expansion. The length of the expanded allele in 3 unaffected FRA12A carriers was 650–850 bp. In the two affected patients from 2 families with FRA12A, the length of the expanded allele was ∼1,050-1,150 bp. 70 controls used to determine the "normal" repeat range. Sources: Other |
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| Mendeliome v0.5601 | CANVAS_ACAGG |
Bryony Thompson changed review comment from: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats. Sources: Literature; to: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified homozygous in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats. Sources: Literature |
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| Mendeliome v0.5600 | CANVAS_ACAGG |
Bryony Thompson STR: CANVAS_ACAGG was added STR: CANVAS_ACAGG was added to Mendeliome. Sources: Literature Mode of inheritance for STR: CANVAS_ACAGG was set to BIALLELIC, autosomal or pseudoautosomal Publications for STR: CANVAS_ACAGG were set to 33103729 Phenotypes for STR: CANVAS_ACAGG were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome; fasciculations; elevated serum creatine kinase levels; denervation Review for STR: CANVAS_ACAGG was set to AMBER Added comment: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats. Sources: Literature |
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| Mendeliome v0.5598 | CANVAS |
Bryony Thompson STR: CANVAS was added STR: CANVAS was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: CANVAS was set to BIALLELIC, autosomal or pseudoautosomal Publications for STR: CANVAS were set to 30926972; 32851396 Phenotypes for STR: CANVAS were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575 Review for STR: CANVAS was set to GREEN STR: CANVAS was marked as clinically relevant Added comment: Simple tandem repeat (AAAAG)11 replaced with (AAGGG)n in intron 2 of RFC1. Loss of function is not the mechanism of disease. Maori population-specific CANVAS configuration (AAAGG)10-25(AAGGG)exp. (AAAGG)n repeat alone is not pathogenic. Sources: Expert list |
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| Mendeliome v0.5593 | RNASEH2C | Zornitza Stark Mode of inheritance for gene: RNASEH2C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5587 | RAP1A | Zornitza Stark Mode of inheritance for gene: RAP1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5583 | RAP1B | Zornitza Stark edited their review of gene: RAP1B: Added comment: Another individual with de novo missense reported from a cohort of Kabuki-like patients but note facial gestalt was not typical.; Changed rating: GREEN; Changed publications: 32627184, 26280580 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5581 | RAP1B | Zornitza Stark Mode of inheritance for gene: RAP1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5579 | EMC10 |
Zornitza Stark gene: EMC10 was added gene: EMC10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EMC10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EMC10 were set to 32869858 Phenotypes for gene: EMC10 were set to Intellectual disability Review for gene: EMC10 was set to RED Added comment: Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders. One Saudi family with 2 affected individuals with mild ID, speech delay, and GDD. WES and Sanger sequencing revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 . Variant segregated within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients. Sources: Literature |
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| Mendeliome v0.5577 | FBXO28 |
Zornitza Stark gene: FBXO28 was added gene: FBXO28 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FBXO28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBXO28 were set to 33280099 Phenotypes for gene: FBXO28 were set to Developmental and epileptic encephalopathy Review for gene: FBXO28 was set to GREEN Added comment: Nine new individuals with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and all 10 known cases reviewed to delineate the phenotypic spectrum. All had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features. Sources: Literature |
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| Mendeliome v0.5576 | CFAP52 |
Zornitza Stark gene: CFAP52 was added gene: CFAP52 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP52 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP52 were set to 25469542; 33139725 Phenotypes for gene: CFAP52 were set to Heterotaxy Review for gene: CFAP52 was set to GREEN Added comment: Five unrelated families and functional data. Sources: Literature |
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| Mendeliome v0.5575 | CFAP45 |
Zornitza Stark gene: CFAP45 was added gene: CFAP45 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP45 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP45 were set to 33139725 Phenotypes for gene: CFAP45 were set to Situs inversus; asthenospermia Review for gene: CFAP45 was set to GREEN Added comment: Three unrelated individuals reported with bi-alleic LOF variants, mouse model recapitulated phenotype. Sources: Literature |
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| Mendeliome v0.5574 | CLCN6 | Zornitza Stark Mode of inheritance for gene: CLCN6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5568 | GDF6 | Zornitza Stark Mode of inheritance for gene: GDF6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5567 | VPS4A |
Kristin Rigbye changed review comment from: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." Sources: Literature; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." |
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| Mendeliome v0.5567 | VPS4A |
Elena Savva changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." |
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| Mendeliome v0.5567 | VPS4A | Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5567 | VPS4A | Elena Savva Mode of pathogenicity for gene: VPS4A was changed from Other to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5567 | VPS4A | Elena Savva Mode of pathogenicity for gene: VPS4A was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5558 | VPS4A |
Kristin Rigbye gene: VPS4A was added gene: VPS4A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VPS4A were set to PMID: 33186543; 33186545 Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder Review for gene: VPS4A was set to GREEN Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." Sources: Literature |
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| Mendeliome v0.5557 | AGO2 |
Zornitza Stark gene: AGO2 was added gene: AGO2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AGO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AGO2 were set to 33199684 Phenotypes for gene: AGO2 were set to Intellectual disability Review for gene: AGO2 was set to GREEN Added comment: 21 individuals reported, five variants (p.L192P, p.G201V, p.T357M, p.M364T, p.C751Y) were recurrent. Variable ID. Sources: Literature |
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| Mendeliome v0.5556 | DAAM2 |
Ain Roesley gene: DAAM2 was added gene: DAAM2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DAAM2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DAAM2 were set to steroid-resistant nephrotic syndrome (SRNS) Penetrance for gene: DAAM2 were set to unknown Review for gene: DAAM2 was set to GREEN Added comment: - steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis on histologic analysis of kidney biopsies and foot process effacement shown by electron microscopy (authors have suggested the term nephrotic syndrome type 22 (NPHS22)) - 4 unrelated families, 3 of which were consanguineous - 4 unique missense and 1 stop - in vitro studies done for the missense variants Sources: Literature |
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| Mendeliome v0.5555 | RRP7A |
Zornitza Stark gene: RRP7A was added gene: RRP7A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RRP7A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RRP7A were set to 33199730 Phenotypes for gene: RRP7A were set to Microcephaly Review for gene: RRP7A was set to AMBER Added comment: 10 affected individuals from a single large consanguineous family where bi-allelic variant segregated with severe microcephaly (-6-8SD), variable ID. Supportive functional data from mouse and zebrafish. Sources: Literature |
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| Mendeliome v0.5554 | BICRA |
Paul De Fazio gene: BICRA was added gene: BICRA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BICRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BICRA were set to 33232675 Phenotypes for gene: BICRA were set to Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features Review for gene: BICRA was set to GREEN gene: BICRA was marked as current diagnostic Added comment: 12 individuals reported, 11 de novo (1 not resolved), "with neurodevelopmental phenotypes—developmental delay (HP:0001263), intellectual disability (HP:0001249), autism spectrum disorder (HP:0000729), and/or behavioral phenotypes (HP:0000708)—and variable structural birth defects and dysmorphic features". Mostly LoF or gene deletions, but 2 missense reported. Zebrafish model supports the gene-disease association. Sources: Literature |
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| Mendeliome v0.5554 | HS2ST1 |
Ain Roesley gene: HS2ST1 was added gene: HS2ST1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HS2ST1 were set to 33159882 Penetrance for gene: HS2ST1 were set to unknown Review for gene: HS2ST1 was set to GREEN Added comment: - 4 affected from 3 unrelated families - 3 unique missense and 2 PTCs - Developmental Delay, Corpus Callosum Hypoplasia or Aplasia, and Skeletal and Renal Abnormalities Sources: Literature |
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| Mendeliome v0.5553 | KDM4B |
Kristin Rigbye gene: KDM4B was added gene: KDM4B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KDM4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM4B were set to PMID: 33232677 Phenotypes for gene: KDM4B were set to Global developmental delay, intellectual disability and neuroanatomical defects Review for gene: KDM4B was set to GREEN Added comment: Nine individuals with mono-allelic de novo or inherited variants in KDM4B. All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had anomalies on brain imaging ranging from agenesis of the corpus callosum with hydrocephalus to cystic formations, abnormal hippocampi, and polymicrogyria. In a knockout mouse the total brain volume was significantly reduced with decreased size of the hippocampal dentate gyrus, partial agenesis of the corpus callosum, and ventriculomegaly. Sources: Literature |
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| Mendeliome v0.5553 | MINPP1 |
Zornitza Stark gene: MINPP1 was added gene: MINPP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MINPP1 were set to 33257696 Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia Review for gene: MINPP1 was set to GREEN Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI. Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions. Sources: Literature |
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| Mendeliome v0.5552 | UNC45B |
Paul De Fazio gene: UNC45B was added gene: UNC45B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UNC45B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC45B were set to 33217308 Phenotypes for gene: UNC45B were set to Progressive Myopathy with Eccentric Cores Review for gene: UNC45B was set to GREEN gene: UNC45B was marked as current diagnostic Added comment: 10 individuals from 8 families reported with biallelic variants clinically manifesting with childhood-onset, progressive proximal and axial muscle weakness and various degrees of respiratory insufficiency. 4 missense variants and a +5 splice variant reported, p.Arg754Gln is recurrent. Functional studies support pathogenicity. Sources: Literature |
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| Mendeliome v0.5550 | DNAJB11 | Zornitza Stark Mode of inheritance for gene: DNAJB11 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5547 | HHAT |
Zornitza Stark gene: HHAT was added gene: HHAT was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HHAT were set to 24784881; 30912300 Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome 600092 Review for gene: HHAT was set to AMBER Added comment: Two unrelated families reported. Clinical features include progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia. Sources: Expert list |
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| Mendeliome v0.5543 | H3F3B | Zornitza Stark Mode of inheritance for gene: H3F3B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5539 | H3F3A | Zornitza Stark Mode of inheritance for gene: H3F3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5535 | ALDH7A1 | Zornitza Stark Mode of inheritance for gene: ALDH7A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5532 | PRPS1 | Zornitza Stark Mode of pathogenicity for gene: PRPS1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5531 | PRPS1 | Zornitza Stark Mode of inheritance for gene: PRPS1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5528 | HIVEP2 | Zornitza Stark Mode of inheritance for gene: HIVEP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5526 | YIPF5 |
Zornitza Stark gene: YIPF5 was added gene: YIPF5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIPF5 were set to 33164986 Phenotypes for gene: YIPF5 were set to Neonatal diabetes; microcephaly; seizures Review for gene: YIPF5 was set to GREEN Added comment: Six individuals from 5 unrelated consanguineous families reported with bi-allelic variants in this gene and neonatal/early-onset diabetes, severe microcephaly, and epilepsy. Functional data supports gene-disease association. Sources: Literature |
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| Mendeliome v0.5524 | TFE3 | Zornitza Stark Mode of inheritance for gene: TFE3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5521 | SLC38A8 | Zornitza Stark Mode of inheritance for gene: SLC38A8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5517 | TONSL | Zornitza Stark Mode of inheritance for gene: TONSL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5512 | NPPA | Zornitza Stark Mode of inheritance for gene: NPPA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5510 | FOXA2 |
Zornitza Stark gene: FOXA2 was added gene: FOXA2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FOXA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXA2 were set to 29329447; 28973288; 11445544 Phenotypes for gene: FOXA2 were set to Hyperinsulinaemia Review for gene: FOXA2 was set to GREEN Added comment: At least two families reported and functional data. Sources: Expert Review |
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| Mendeliome v0.5507 | FKBP8 |
Eleanor Williams gene: FKBP8 was added gene: FKBP8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FKBP8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FKBP8 were set to 32969478 Phenotypes for gene: FKBP8 were set to spina bifida HP:0002414 Review for gene: FKBP8 was set to AMBER Added comment: Not associated with a phenotype in OMIM. PMID: 32969478 - Tian et al 2020 - performed Sanger sequencing of FKBP8 on DNA samples from 472 spina bifida (SB) affected fetuses and 565 unaffected controls. 5 different rare heterozygous variants (MAF ≤ 0.001) were identified among the SB patients, while no deleterious rare variants were identified in the controls. 4 of the variants are missense, the other is a stop-gain. 2 cases were in white-Hispanic patients while the other 3 were non-white Hispanic. Functional studies showed that p.Glu140* affected FKBP8 localization to the mitochondria and impaired its interaction with BCL2 ultimately leading to an increase in cellular apoptosis. p.Ser3Leu, p.Lys315Asn and p.Ala292Ser variants decreased FKBP8 protein level. Gene expression was studied in mouse Fkbp8-/- embryos and found to be abnormal. Previous mouse models have shown neural tube defects. Sufficient cases to rate green, but only the FKBP8 gene looked at so perhaps some caution required while further evidence is gathered. Sources: Literature |
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| Mendeliome v0.5507 | CAPN15 |
Eleanor Williams gene: CAPN15 was added gene: CAPN15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAPN15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAPN15 were set to 32885237 Phenotypes for gene: CAPN15 were set to microphthalmia HP:0000568; coloboma HP:0000589 Review for gene: CAPN15 was set to GREEN Added comment: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families). Sources: Literature |
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| Mendeliome v0.5505 | MYF5 | Zornitza Stark Mode of inheritance for gene: MYF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5502 | COX16 |
Bryony Thompson gene: COX16 was added gene: COX16 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: COX16 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX16 were set to 33169484 Phenotypes for gene: COX16 were set to Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis Review for gene: COX16 was set to AMBER Added comment: 2 unrelated patients with the same homozygous (non-consanguineous) nonsense variant c.244C>T (p.Arg82*), and isolated complex IV deficiency present in both patient fibroblasts/skeletal muscle biopsy. COX16 is involved in the biogenesis of complex IV, the terminal complex of the mitochondrial respiratory chain (RC) Sources: Literature |
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| Mendeliome v0.5500 | KCNJ18 |
Zornitza Stark gene: KCNJ18 was added gene: KCNJ18 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KCNJ18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNJ18 were set to 20074522; 27008341 Phenotypes for gene: KCNJ18 were set to {Thyrotoxic periodic paralysis, susceptibility to, 2}, MIM# 613239 Review for gene: KCNJ18 was set to RED Added comment: Six variants reported in original publication, however note lack of segregation data and limited functional data. Subsequently, concerns raised about high nucleotide sequence homology between multiple potassium channel genes, with variant misattribution. Sources: Expert Review |
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| Mendeliome v0.5497 | DPM3 | Zornitza Stark Mode of inheritance for gene: DPM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5494 | B3GAT3 | Zornitza Stark Mode of inheritance for gene: B3GAT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5491 | SLC10A7 | Zornitza Stark Mode of inheritance for gene: SLC10A7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5484 | GPAA1 | Zornitza Stark Mode of inheritance for gene: GPAA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5481 | ATP7A | Zornitza Stark Mode of inheritance for gene: ATP7A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5478 | PEX1 | Zornitza Stark Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5473 | TMEM218 |
Bryony Thompson gene: TMEM218 was added gene: TMEM218 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM218 were set to https://doi.org/10.1016/j.xhgg.2020.100016; 25161209 Phenotypes for gene: TMEM218 were set to Joubert syndrome; retinal dystrophy; polycystic kidneys; occipital encephalocele Review for gene: TMEM218 was set to GREEN Added comment: 11 cases in 6 families with homozygous or compound heterozygous missense and nonsense (1) variants, with a Joubert/Meckel syndrome phenotype. Clinical features included the molar tooth sign (N=2), occipital encephalocele (N=5, all fetuses), retinal dystrophy (N=4, all living individuals), polycystic kidneys (N=2), and polydactyly (N=2), without liver involvement. A null mouse model had nephronophthisis and retinal degeneration. No OMIM entry. Sources: Literature |
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| Mendeliome v0.5472 | AGBL1 |
Zornitza Stark gene: AGBL1 was added gene: AGBL1 was added to Mendeliome. Sources: Expert Review disputed tags were added to gene: AGBL1. Mode of inheritance for gene: AGBL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AGBL1 were set to 24094747; 31555324 Phenotypes for gene: AGBL1 were set to Corneal dystrophy, Fuchs endothelial, 8, MIM# 615523 Review for gene: AGBL1 was set to RED Added comment: Gene disease association first reported in 2013 in PMID 24094747, in a large multigenerational family. However, note the variant reported, p.Arg1028Ter is present in over 400 hets in gnomad. Another variant reported in same paper, p.Cys990Ser in three unrelated individuals, is present in over 300 hets in gnomad and 1 hom. Two further variants reported in PMID 31555324, one is missense, p.Arg748His, present in 60 hets, and the other, p.Arg1028Ter, is present is the variant identified in the previous publication, present in over 400 hets. These variant frequencies are out of keeping for a rare disorder. Sources: Expert Review |
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| Mendeliome v0.5470 | TLE6 |
Zornitza Stark gene: TLE6 was added gene: TLE6 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: TLE6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TLE6 were set to 26537248; 31897846 Phenotypes for gene: TLE6 were set to Preimplantation embryonic lethality, MIM# 616814 Review for gene: TLE6 was set to GREEN Added comment: At least 5 individuals reported with bi-allelic variants and early embryonic lethality. Sources: Expert Review |
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| Mendeliome v0.5467 | OGT | Zornitza Stark Mode of inheritance for gene: OGT was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5464 | EXTL3 | Zornitza Stark Mode of inheritance for gene: EXTL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5462 | SSR3 |
Zornitza Stark gene: SSR3 was added gene: SSR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SSR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SSR3 were set to 30945312 Phenotypes for gene: SSR3 were set to Congenital disorder of glycosylation Review for gene: SSR3 was set to AMBER Added comment: Single individual reported with an unsolved type I CDG, intellectual disability, homozygous LOF variant in SSR3, supportive functional evidence. Sources: Literature |
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| Mendeliome v0.5461 | LCP2 |
Zornitza Stark gene: LCP2 was added gene: LCP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LCP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LCP2 were set to 33231617 Phenotypes for gene: LCP2 were set to Severe combined immunodeficiency Review for gene: LCP2 was set to RED Added comment: Infant with bi-allelic variants in this gene and early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation. Sources: Literature |
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| Mendeliome v0.5458 | DPM2 | Zornitza Stark edited their review of gene: DPM2: Added comment: Further unrelated individual reported, main clinical features were truncal hypotonia, hypertonicity, congenital heart defects, intellectual disability, and generalized muscle wasting.; Changed rating: GREEN; Changed publications: 23109149, 33129689 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5456 | ATP6V0A2 | Zornitza Stark Mode of inheritance for gene: ATP6V0A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5453 | ALG9 | Zornitza Stark Mode of inheritance for gene: ALG9 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5450 | ALG8 | Zornitza Stark Mode of inheritance for gene: ALG8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5449 | ALG8 | Zornitza Stark changed review comment from: Review of 15 reported individuals in PMID: 26066342: multiple prenatal abnormalities were present in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13.; to: Bi-allelic variants and CDG: Review of 15 reported individuals in PMID: 26066342. Multiple prenatal abnormalities were present in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5447 | ALG8 | Zornitza Stark Mode of inheritance for gene: ALG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5444 | ALG3 | Zornitza Stark Mode of inheritance for gene: ALG3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5437 | HOXA4 | Zornitza Stark Mode of inheritance for gene: HOXA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5433 | ASTE1 | Zornitza Stark Mode of inheritance for gene: ASTE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5429 | SMARCA1 | Zornitza Stark Mode of inheritance for gene: SMARCA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5424 | TCHH | Zornitza Stark Mode of inheritance for gene: TCHH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5420 | CRTAP | Zornitza Stark Mode of inheritance for gene: CRTAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5417 | USP9X | Zornitza Stark Mode of inheritance for gene: USP9X was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5414 | ALG6 | Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5410 | RORB | Zornitza Stark Mode of inheritance for gene: RORB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5408 | MYL9 |
Zornitza Stark gene: MYL9 was added gene: MYL9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MYL9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYL9 were set to 29453416; 33031641 Phenotypes for gene: MYL9 were set to Megacystis-microcolon-intestinal hypoperistalsis syndrome Review for gene: MYL9 was set to AMBER Added comment: Two unrelated families reported. Sources: Literature |
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| Mendeliome v0.5403 | PHYKPL | Zornitza Stark Mode of inheritance for gene: PHYKPL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5398 | POLE | Zornitza Stark Mode of pathogenicity for gene: POLE was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5397 | POLE | Zornitza Stark Mode of inheritance for gene: POLE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5396 | POLE | Zornitza Stark Tag deep intronic tag was added to gene: POLE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5394 | OFD1 | Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5392 | NARS | Zornitza Stark Tag new gene name tag was added to gene: NARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5392 | ANAPC1 | Zornitza Stark Tag deep intronic tag was added to gene: ANAPC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5390 | DZIP1 | Zornitza Stark Mode of inheritance for gene: DZIP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5387 | DZIP1 |
Zornitza Stark gene: DZIP1 was added gene: DZIP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DZIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DZIP1 were set to 31118289 Phenotypes for gene: DZIP1 were set to Mitral valve prolapse Review for gene: DZIP1 was set to AMBER Added comment: One large 4-generation family reported, where missense variant segregated with disease. Two additional individuals identified from a cohort. All variants present at low frequency in population databases. Mouse model recapitulated phenotype. Sources: Literature |
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| Mendeliome v0.5385 | ADH5 |
Zornitza Stark gene: ADH5 was added gene: ADH5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADH5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADH5 were set to 33147438 Phenotypes for gene: ADH5 were set to Aplastic anaemia; myelodysplasia; short stature Review for gene: ADH5 was set to GREEN Added comment: 7 individuals reported with bi-allelic variants in this gene and a Fanconi syndrome-like phenotype. All had aplastic anaemia, 4 developed a myelodysplastic syndrome, and one developed AML. Short stature and abnormal skin pigmentation were additional features. Note, all also had the ALDH2*2 allele, which is common in East Asian populations, and may be contributory. Extensive experimental data. Sources: Literature |
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| Mendeliome v0.5382 | NPHS2 | Zornitza Stark Mode of inheritance for gene: NPHS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5381 | LRIF1 |
Bryony Thompson changed review comment from: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus. Sources: Literature; to: A single consanguineous case with a homozygous truncating variant, and D4Z4 repeat of 13 units on a 4qA haplotype (permissive haplotype). DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus. Sources: Literature |
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| Mendeliome v0.5380 | LRIF1 |
Bryony Thompson gene: LRIF1 was added gene: LRIF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LRIF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRIF1 were set to 32467133 Phenotypes for gene: LRIF1 were set to Facioscapulohumeral muscular dystrophy Review for gene: LRIF1 was set to AMBER Added comment: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus. Sources: Literature |
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| Mendeliome v0.5374 | RLIM | Zornitza Stark Mode of inheritance for gene: RLIM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5372 | DNAH2 |
Zornitza Stark gene: DNAH2 was added gene: DNAH2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DNAH2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH2 were set to 30811583 Phenotypes for gene: DNAH2 were set to Spermatogenic failure 45, MIM# 619094 Review for gene: DNAH2 was set to GREEN Added comment: Three unrelated families reported. Sources: Expert list |
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| Mendeliome v0.5369 | FGFR1 | Zornitza Stark Tag somatic tag was added to gene: FGFR1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5367 | FGFR1 | Zornitza Stark Mode of pathogenicity for gene: FGFR1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5366 | FGFR1 | Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5363 | B4GALT7 | Zornitza Stark Mode of inheritance for gene: B4GALT7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5362 | B4GALT7 | Zornitza Stark Tag founder tag was added to gene: B4GALT7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5359 | KCNQ2 | Zornitza Stark Mode of pathogenicity for gene: KCNQ2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5358 | KCNQ2 | Zornitza Stark Mode of inheritance for gene: KCNQ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5356 | ADAR | Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5351 | SCD5 |
Zornitza Stark gene: SCD5 was added gene: SCD5 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SCD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SCD5 were set to 31972369 Phenotypes for gene: SCD5 were set to Deafness, autosomal dominant 79, MIM#619086 Review for gene: SCD5 was set to RED Added comment: Single 5-generation family reported with a missense variant segregating in 19 affected individuals. Variant is found at a low frequency in ExAC. Sources: Expert list |
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| Mendeliome v0.5345 | OCLN | Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5342 | JAM3 | Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5339 | NCKAP1 | Zornitza Stark Mode of inheritance for gene: NCKAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5336 | ACAD9 | Zornitza Stark Mode of inheritance for gene: ACAD9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5332 | ALDOB | Zornitza Stark Mode of inheritance for gene: ALDOB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5329 | ARL2 |
Zornitza Stark gene: ARL2 was added gene: ARL2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARL2 were set to 30945270 Phenotypes for gene: ARL2 were set to Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma-1 (MRCS1), MIM#619082 Review for gene: ARL2 was set to RED Added comment: Single family reported, missense variant segregating with structural eye abnormalities in 4 individuals (father and three daughters). Sources: Expert list |
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| Mendeliome v0.5324 | UNC80 | Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5323 | ZFHX4 | Zornitza Stark Tag SV/CNV tag was added to gene: ZFHX4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5320 | CARD8 |
Zornitza Stark gene: CARD8 was added gene: CARD8 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CARD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CARD8 were set to 29408806 Phenotypes for gene: CARD8 were set to Inflammatory bowel disease-30, MIM#619079 Review for gene: CARD8 was set to RED Added comment: Two individuals from one family reported segregating a missense variant, dominant negative effect postulated. Sources: Expert list |
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| Mendeliome v0.5315 | ZFHX4 |
Bryony Thompson gene: ZFHX4 was added gene: ZFHX4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZFHX4 were set to 33057194 Phenotypes for gene: ZFHX4 were set to Developmental disorders Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5313 | UPF1 |
Bryony Thompson gene: UPF1 was added gene: UPF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UPF1 were set to 33057194 Phenotypes for gene: UPF1 were set to Developmental disorders Review for gene: UPF1 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (1 frameshift, 11 missense, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5311 | U2AF2 |
Bryony Thompson gene: U2AF2 was added gene: U2AF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: U2AF2 were set to 33057194 Phenotypes for gene: U2AF2 were set to Developmental disorders Review for gene: U2AF2 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 8 missense, 1 synoymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5307 | TCF7L2 | Bryony Thompson Mode of inheritance for gene: TCF7L2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5304 | SRRM2 |
Bryony Thompson gene: SRRM2 was added gene: SRRM2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SRRM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SRRM2 were set to 33057194 Phenotypes for gene: SRRM2 were set to Developmental disorders Review for gene: SRRM2 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 28 de novo variants (11 frameshift, 7 missense, 1 splice acceptor, 5 stopgain, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5302 | SPEN |
Bryony Thompson gene: SPEN was added gene: SPEN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPEN were set to 33057194 Phenotypes for gene: SPEN were set to Developmental disorders Review for gene: SPEN was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5300 | SATB1 |
Bryony Thompson gene: SATB1 was added gene: SATB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SATB1 were set to 33057194 Phenotypes for gene: SATB1 were set to Developmental disorders Review for gene: SATB1 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5298 | RAB14 |
Bryony Thompson gene: RAB14 was added gene: RAB14 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAB14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB14 were set to 33057194 Phenotypes for gene: RAB14 were set to Developmental disorders Review for gene: RAB14 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (1 in-frame, 7 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5296 | PSMC5 |
Bryony Thompson gene: PSMC5 was added gene: PSMC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PSMC5 were set to 33057194 Phenotypes for gene: PSMC5 were set to Developmental disorders Review for gene: PSMC5 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 9 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5293 | PRPF8 | Bryony Thompson Mode of inheritance for gene: PRPF8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5290 | MSL2 |
Bryony Thompson gene: MSL2 was added gene: MSL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MSL2 were set to 31332282; 33057194 Phenotypes for gene: MSL2 were set to Developmental disorders; autism Review for gene: MSL2 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 13 de novo variants (9 frameshift, 4 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). PMID: 31332282 - candidate gene in a single autism study, with recurrent de novo variants in a potential oligogenic model Sources: Literature |
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| Mendeliome v0.5288 | MMGT1 |
Bryony Thompson gene: MMGT1 was added gene: MMGT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MMGT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MMGT1 were set to 33057194 Phenotypes for gene: MMGT1 were set to Developmental disorders Review for gene: MMGT1 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 3 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5285 | MIB1 | Bryony Thompson Mode of inheritance for gene: MIB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5283 | MFN2 | Bryony Thompson Mode of inheritance for gene: MFN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5281 | KCNK3 | Bryony Thompson Mode of inheritance for gene: KCNK3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5279 | HNRNPD |
Bryony Thompson gene: HNRNPD was added gene: HNRNPD was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HNRNPD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPD were set to 33057194 Phenotypes for gene: HNRNPD were set to Developmental disorders Review for gene: HNRNPD was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (5 frameshift, 1 missense, 1 splice acceptor, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5276 | PLXND1 |
Zornitza Stark gene: PLXND1 was added gene: PLXND1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLXND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLXND1 were set to 26068067 Phenotypes for gene: PLXND1 were set to Möbius syndrome Review for gene: PLXND1 was set to GREEN Added comment: De novo variants in 3 unrelated individuals with Moebius syndrome with some functional evidence. Sources: Literature |
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| Mendeliome v0.5274 | MYMK | Zornitza Stark Tag founder tag was added to gene: MYMK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5273 | ECEL1 | Zornitza Stark Mode of inheritance for gene: ECEL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5272 | PRKG2 |
Arina Puzriakova gene: PRKG2 was added gene: PRKG2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRKG2 were set to 33106379 Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia Review for gene: PRKG2 was set to GREEN Added comment: - PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones. Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper). Sources: Literature |
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| Mendeliome v0.5270 | FOXP4 |
Zornitza Stark gene: FOXP4 was added gene: FOXP4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXP4 were set to 33110267 Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities Review for gene: FOXP4 was set to GREEN Added comment: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays. Sources: Literature |
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| Mendeliome v0.5268 | ASAH1 | Zornitza Stark Mode of inheritance for gene: ASAH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5262 | ALK | Zornitza Stark Mode of inheritance for gene: ALK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5258 | DHX32 |
Dean Phelan gene: DHX32 was added gene: DHX32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DHX32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHX32 were set to PMID: 32989326 Phenotypes for gene: DHX32 were set to Intellectual disability, spastic diplegia, dystonia, brain abnormalities Review for gene: DHX32 was set to AMBER Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two unrelated patients with intellectual disability, one with spastic diplegia, and the other characterised as generalised dystonia. Brain abnormalities were identified also. Sources: Literature |
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| Mendeliome v0.5257 | FBXO31 | Zornitza Stark Mode of pathogenicity for gene: FBXO31 was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5256 | FBXO31 | Zornitza Stark Mode of inheritance for gene: FBXO31 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5252 | NHLRC2 | Zornitza Stark Mode of inheritance for gene: NHLRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5251 | RHOB |
Crystle Lee gene: RHOB was added gene: RHOB was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RHOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RHOB were set to 32989326 Phenotypes for gene: RHOB were set to Cerebral Palsy (PMID:32989326) Mode of pathogenicity for gene: RHOB was set to Other Review for gene: RHOB was set to AMBER Added comment: Candidate disease-causing gene for CP. Recurrent de novo missense variant reported in 2 unrelated families with supporting functional studies. Sources: Expert list |
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| Mendeliome v0.5250 | CTLA4 | Zornitza Stark Mode of inheritance for gene: CTLA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5247 | VIM | Zornitza Stark Mode of inheritance for gene: VIM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5243 | ITPR3 |
Zornitza Stark gene: ITPR3 was added gene: ITPR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ITPR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ITPR3 were set to 32949214 Phenotypes for gene: ITPR3 were set to Charcot-Marie-Tooth disease Review for gene: ITPR3 was set to AMBER Added comment: Two unrelated families reported: variant segregated in four affected individuals in one family and was de novo in the second family where there was a single affected person. Some evidence for dominant-negative effect. Sources: Literature |
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| Mendeliome v0.5240 | AMOTL1 |
Zornitza Stark gene: AMOTL1 was added gene: AMOTL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AMOTL1 were set to 33026150 Phenotypes for gene: AMOTL1 were set to Cleft lip and palate; imperforate anus; dysmorphism Review for gene: AMOTL1 was set to RED Added comment: Two unrelated families reported. In one, the variant was identified in parent and child who had orofacial cleft and cardiac abnormalities. Second report in PMID 33026150, de novo missense variant and cleft lip/palate, imperforate anus and dysmorphism. Mouse model does not recapitulate phenotype. Sources: Literature |
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| Mendeliome v0.5238 | KIRREL1 |
Zornitza Stark gene: KIRREL1 was added gene: KIRREL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIRREL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIRREL1 were set to 31472902 Phenotypes for gene: KIRREL1 were set to Steroid-resistant nephrotic syndrome Review for gene: KIRREL1 was set to AMBER Added comment: Two unrelated families reported with bi-allelic variants and limited functional data. Sources: Literature |
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| Mendeliome v0.5236 | GFRA1 |
Zornitza Stark gene: GFRA1 was added gene: GFRA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GFRA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GFRA1 were set to 33020172 Phenotypes for gene: GFRA1 were set to Renal agenesis Review for gene: GFRA1 was set to AMBER Added comment: Two unrelated families reported with bi-allelic LOF variants identified in individuals with bilateral renal agenesis. GFRA1 gene encodes a receptor on the Wolffian duct that regulates ureteric bud outgrowth in the development of a functional renal system. Sources: Literature |
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| Mendeliome v0.5234 | GIGYF1 |
Bryony Thompson gene: GIGYF1 was added gene: GIGYF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GIGYF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GIGYF1 were set to 33057194 Phenotypes for gene: GIGYF1 were set to Developmental disorder Review for gene: GIGYF1 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5232 | FBXW7 |
Bryony Thompson gene: FBXW7 was added gene: FBXW7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBXW7 were set to 33057194 Phenotypes for gene: FBXW7 were set to Developmental disorder Review for gene: FBXW7 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 12 de novo missense and 1 de novo synonymous variant identified in ~10,000 cases with developmental disorders (no other phenotype info provided) Sources: Literature |
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| Mendeliome v0.5229 | PRKAR1B |
Konstantinos Varvagiannis gene: PRKAR1B was added gene: PRKAR1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRKAR1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040 Phenotypes for gene: PRKAR1B were set to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure Penetrance for gene: PRKAR1B were set to unknown Review for gene: PRKAR1B was set to AMBER Added comment: Please consider inclusion of this gene with amber rating pending publication of the preprint and/or additional evidence. Marbach et al. (2020 - medRxiv : https://doi.org/10.1101/2020.09.10.20190314 - last author : C. Schaaf) report 6 unrelated individuals with heterozygous missense PRKAR1B variants. All presented formal ASD diagnosis (6/6), global developmental delay (6/6) and intellectual disability (all - formal evaluations were lacking though). Additional features included neurologic anomalies (movement disorders : dyspraxia, apraxia, clumsiness in all, with tremor/dystonia or involuntary movements as single occurrences). Three displayed high pain tolerance. Regression in speech was a feature in two. Additional behavior anomalies included ADHD (4-5/6) or aggression (3/6). There was no consistent pattern of malformations, physical anomalies or facial features (with the exception of uplsanted palpebral fissures reported in 4). 3 different missense variants were identified (NM_00116470:c.1003C>T - p.Arg335Trp, c.586G>A - p.Glu196Lys, c.500_501delAAinsTT - p.Gln167Leu) with Arg355Trp being a recurrent one within this cohort (4/6 subjects). A possible splicing effect may apply for the MNV. All variants are absent from gnomAD and the SNVs had CADD scores > 24. In all cases were parental samples were available (5/6), the variant had occurred as a de novo event. Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. As the authors comment, the RIβ subunit is primarily expressed in brain with higher expression in cortex and hypothalamus. The functional consequences of the variants at cellular level were not studied. Previous studies have demonstrated that downregulation of RIβ in murine hippocampal cultures, reduced phosphorylation of CREB, a transcription factor involved in long-term memory formation. The authors speculate that a similar effect on cAMP/PKA/CREB cascade may mediate the cognitive effects in humans. RIβ deficient mice also display diminished nociceptive pain, similar to the human phenotype. [Several refs provided]. The authors cite the study by Kaplanis et al (2020 - PMID: 33057194), where in a large sample of 31,058 trio exomes of children with developmental disorders, PRKAR1B was among the genes with significant enrichment for de novo missense variants. [The gene has a pLI score of 0.18 in gnomAD / o/e = 0.26 - so pLoF variants may not be deleterious]. Please note that a specific PRKAR1B variant (NM_002735.2:c.149T>G - p.Leu50Arg) has been previous reported to segregate with a late-onset neurodegenerative disorder characterized by dementia and/or parkinsonism within a large pedigree with 12 affected individuals [Wong et al 2014 - PMID: 25414040]. Sources: Literature |
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| Mendeliome v0.5227 | NR1H4 | Zornitza Stark Mode of inheritance for gene: NR1H4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5224 | PTF1A | Zornitza Stark Mode of inheritance for gene: PTF1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5222 | MPP5 |
Konstantinos Varvagiannis gene: MPP5 was added gene: MPP5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MPP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MPP5 were set to 33073849 Phenotypes for gene: MPP5 were set to Global developmental delay; Intellectual disability; Delayed speech and language development; Developmental regression; Behavioral abnormality Penetrance for gene: MPP5 were set to unknown Review for gene: MPP5 was set to GREEN Added comment: Sterling et al (2020 - PMID: 33073849) provide information on the phenotype of 3 individuals with de novo MPP5 variants. Common features included global developmental delay, intellectual disability (3/3 - severe in 2/3), speech delay/regression (the latter in at least 2) and behavioral abnormalities. Variable other features were reported, among others microcephaly (1/3), abnormal vision (1/3 : CVI, retinal dystrophy, nystagmus), brain MRI abnormalities (2/3), late-onset seizures (1/3). These subjects displayed variable and non-specific dysmorphic features. All were investigated by exome sequencing (previous investigations not mentioned). One subject was found to harbor a de novo mosaic (5/25 reads) stopgain variant, further confirmed by Sanger sequencing [NM_022474.4:c.1555C>T - p.(Arg519Ter). The specific variant is reported once in gnomAD (1/251338). Two de novo missense variants were identified in the remaining individuals [c.1289A>G - p.Glu430Gly / c.974A>C - p.His325Pro). All variants had in silico predictions in favor of a deleterious effect (CADD score >24). The authors comment that MPP5 encodes an apical complex protein with asymmetric localization to the apical side of polarized cells. It is expressed in brain, peripheral nervous system and other tissues. MPP5 is a member of the membrane-associated guanylate kinase family of proteins (MAGUK p55 subfamily), determining cell polarity at tight junctions. Previous animal models suggest that complete Mpp5(Pals1) KO in mice leads to near absence of cerebral cortical neurons. Htz KO display reduction in size of cerebral cortex and hippocampus. The gene is expressed in proliferating cell populations of cerebellum and important for establishment cerebellar architecture. Conditional KO of Mpp5(Pals1) in retinal progenitor cells mimics the retinal pathology observed in LCA. [Several refs. provided] The authors studied a heterozygous CNS-specific Mpp5 KO mouse model. These mice presented microcephaly, decreased cerebellar volume and cortical thickness, decreased ependymal cells and Mpp5 at the apical surface of cortical vertrical zone. The proportion of cortical cells undergoing apoptotic cell death was increased. Mice displayed behavioral abnormalities (hyperactivity) and visual deficits, with ERG traces further suggesting retinal blindness. Overall the mouse model was thought to recapitulate the behavioral abnormalities observed in affected subjects as well as individual rare features such as microcephaly and abnormal vision. Haploinsufficiency (rather than a dominant negative effect) is favored as the underlying disease mechanism. This is also in line with a dose dependent effect observed in mice. Sources: Literature |
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| Mendeliome v0.5220 | AKR1D1 | Zornitza Stark Mode of inheritance for gene: AKR1D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5217 | SCYL1 | Zornitza Stark Mode of inheritance for gene: SCYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5214 | SLC30A10 | Zornitza Stark Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5212 | DDX23 |
Bryony Thompson gene: DDX23 was added gene: DDX23 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DDX23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DDX23 were set to 33057194 Phenotypes for gene: DDX23 were set to Developmental disorder Review for gene: DDX23 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 6 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided) Sources: Literature |
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| Mendeliome v0.5210 | ATP6V0A1 |
Bryony Thompson gene: ATP6V0A1 was added gene: ATP6V0A1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP6V0A1 were set to 30842224; 33057194 Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like Review for gene: ATP6V0A1 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided). PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype Sources: Literature |
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| Mendeliome v0.5208 | ARHGAP35 |
Bryony Thompson gene: ARHGAP35 was added gene: ARHGAP35 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARHGAP35 were set to 33057194 Phenotypes for gene: ARHGAP35 were set to Developmental disorder Review for gene: ARHGAP35 was set to AMBER Added comment: Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 16 de novo variants (3 frameshift, 2 in-frame, 10 missense, 1 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature |
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| Mendeliome v0.5206 | AP2S1 | Bryony Thompson Mode of inheritance for gene: AP2S1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5202 | ASCL1 | Zornitza Stark Mode of inheritance for gene: ASCL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5197 | KDELR2 |
Zornitza Stark gene: KDELR2 was added gene: KDELR2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KDELR2 were set to 33053334 Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms Review for gene: KDELR2 was set to GREEN Added comment: 4 families with osteogenesis imperfecta reported with functional studies. Sources: Expert list |
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| Mendeliome v0.5194 | SCN8A | Zornitza Stark Mode of pathogenicity for gene: SCN8A was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5193 | SCN8A | Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5186 | NUS1 | Zornitza Stark Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5183 | COG8 | Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5180 | HBB | Zornitza Stark Mode of inheritance for gene: HBB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5179 | ISPD | Zornitza Stark Tag SV/CNV tag was added to gene: ISPD. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5176 | RAD51D | Zornitza Stark Mode of inheritance for gene: RAD51D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5172 | TPO | Zornitza Stark Mode of inheritance for gene: TPO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5166 | VAC14 | Zornitza Stark Mode of inheritance for gene: VAC14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5161 | COL25A1 | Zornitza Stark Mode of inheritance for gene: COL25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5157 | KIF21A | Zornitza Stark Mode of inheritance for gene: KIF21A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5154 | NDUFAF6 | Zornitza Stark Mode of inheritance for gene: NDUFAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5151 | WNT5A | Zornitza Stark Mode of inheritance for gene: WNT5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5148 | CYP3A4 | Zornitza Stark Mode of pathogenicity for gene: CYP3A4 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5147 | CYP3A4 | Zornitza Stark Mode of inheritance for gene: CYP3A4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5144 | KCTD17 | Zornitza Stark Mode of inheritance for gene: KCTD17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5143 | TAF1 |
Zornitza Stark Tag deep intronic tag was added to gene: TAF1. Tag founder tag was added to gene: TAF1. |
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| Mendeliome v0.5141 | TAF1 | Zornitza Stark Mode of inheritance for gene: TAF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5139 | CTNNA3 |
Bryony Thompson gene: CTNNA3 was added gene: CTNNA3 was added to Mendeliome. Sources: ClinGen Mode of inheritance for gene: CTNNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CTNNA3 were set to 23136403; 21254927; 22421363; 30415094; 31539150 Phenotypes for gene: CTNNA3 were set to Arrhythmogenic right ventricular cardiomyopathy; Arrhythmogenic right ventricular dysplasia, familial, 13 MIM#615616 Review for gene: CTNNA3 was set to AMBER Added comment: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019). PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC. Additional publications identified - PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative. Sources: ClinGen |
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| Mendeliome v0.5137 | UBE3A | Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5136 | UBE3A | Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5133 | CHRNE | Zornitza Stark Mode of inheritance for gene: CHRNE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5130 | COLQ | Zornitza Stark Mode of inheritance for gene: COLQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5123 | APOPT1 | Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5121 | COX4I1 |
Zornitza Stark gene: COX4I1 was added gene: COX4I1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: COX4I1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX4I1 were set to 28766551; 22592081; 31290619 Phenotypes for gene: COX4I1 were set to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060 Review for gene: COX4I1 was set to AMBER Added comment: Two unrelated families reported. Two more variants reported in PMID: 22592081: one is non-coding and the other rare missense, appear to have been identified in separate individuals, i.e. heterozygous in each individual. Sources: Expert list |
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| Mendeliome v0.5116 | PET100 | Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5115 | PET100 | Zornitza Stark Tag founder tag was added to gene: PET100. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5113 | COX20 | Zornitza Stark Mode of inheritance for gene: COX20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5109 | TACO1 | Zornitza Stark Mode of inheritance for gene: TACO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5106 | CNGA2 |
Zornitza Stark gene: CNGA2 was added gene: CNGA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNGA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: CNGA2 were set to 28572688 Phenotypes for gene: CNGA2 were set to Congenital anosmia Review for gene: CNGA2 was set to RED Added comment: Single multiplex family with high-impact variant segregating with anosmia. Sources: Literature |
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| Mendeliome v0.5103 | COX6B1 | Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5102 | PRKACB |
Konstantinos Varvagiannis gene: PRKACB was added gene: PRKACB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRKACB were set to 33058759 Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability Penetrance for gene: PRKACB were set to unknown Mode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PRKACB was set to GREEN Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants. The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD. Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors. Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID. As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes. WES was carried out in all. PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD). PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo. Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt). By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals. As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). Sources: Literature |
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| Mendeliome v0.5102 | PRKACA |
Konstantinos Varvagiannis gene: PRKACA was added gene: PRKACA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRKACA were set to 33058759; 31130284 Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability Penetrance for gene: PRKACA were set to unknown Mode of pathogenicity for gene: PRKACA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PRKACA was set to GREEN Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants. The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD. Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors. Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID. As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes. WES was carried out in all. PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD). PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo. Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt). By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals. As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). Sources: Literature |
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| Mendeliome v0.5100 | SCO1 | Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5097 | COX10 | Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5094 | GFPT1 | Zornitza Stark Mode of inheritance for gene: GFPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5093 | BMP7 |
Zornitza Stark gene: BMP7 was added gene: BMP7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BMP7 were set to 32266521; 24429398 Phenotypes for gene: BMP7 were set to Non-syndromic metopic craniosynostosis Mode of pathogenicity for gene: BMP7 was set to Other Review for gene: BMP7 was set to RED Added comment: Non-syndromic metopic craniosynostosis: PMID 32266521 reports rs6127972 as a susceptibility SNP for non-syndromic metopic craniosynostosis CAKUT: PMID 24429398 1 family with mouse model in large cohort of CAKUT. Sources: Literature |
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| Mendeliome v0.5090 | SMARCC1 |
Zornitza Stark gene: SMARCC1 was added gene: SMARCC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SMARCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCC1 were set to 33077954 Phenotypes for gene: SMARCC1 were set to Congenital hydrocephalus Review for gene: SMARCC1 was set to GREEN Added comment: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort. Sources: Literature |
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| Mendeliome v0.5087 | SLC18A3 | Zornitza Stark Mode of inheritance for gene: SLC18A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5083 | SYT2 | Zornitza Stark Mode of inheritance for gene: SYT2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5080 | CHAT | Zornitza Stark Mode of inheritance for gene: CHAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5079 | ALG2 | Zornitza Stark Tag founder tag was added to gene: ALG2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5077 | ALG2 | Zornitza Stark Mode of inheritance for gene: ALG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5073 | AGRN | Zornitza Stark Mode of inheritance for gene: AGRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5070 | DPH1 | Zornitza Stark Mode of inheritance for gene: DPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5060 | AFF2 |
Zornitza Stark Tag SV/CNV tag was added to gene: AFF2. Tag STR tag was added to gene: AFF2. |
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| Mendeliome v0.5058 | AFF2 | Zornitza Stark Mode of inheritance for gene: AFF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5055 | AUTS2 | Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5055 | AUTS2 | Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5054 | AUTS2 | Zornitza Stark Tag SV/CNV tag was added to gene: AUTS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5052 | ZEB2 | Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5050 | ITSN2 |
Elena Savva gene: ITSN2 was added gene: ITSN2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ITSN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITSN2 were set to PMID: 29773874 Phenotypes for gene: ITSN2 were set to Nephrotic syndrome Review for gene: ITSN2 was set to GREEN Added comment: PMID: 29773874: 2 families (3 patients) with homozygous missense or chet missense/PTC + null mice recapitulating the human phenotype. Functional analysis of all variants shows an inability for Cdc42 activation as shown by wildtype overexpression Sources: Literature |
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| Mendeliome v0.5050 | PI4K2A |
Zornitza Stark gene: PI4K2A was added gene: PI4K2A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PI4K2A were set to 32418222 Phenotypes for gene: PI4K2A were set to Cutis laxa, intellectual disability, movement disorder Review for gene: PI4K2A was set to RED Added comment: Single individual reported with homozygous missense variant and functional data including mouse model. Sources: Literature |
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| Mendeliome v0.5047 | NR5A1 | Zornitza Stark Mode of inheritance for gene: NR5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5044 | HECW2 | Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5043 | HECW2 | Zornitza Stark Mode of inheritance for gene: HECW2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5042 | ARHGEF9 | Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5039 | ZMYND10 | Zornitza Stark Mode of inheritance for gene: ZMYND10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5036 | SPAG1 | Zornitza Stark Mode of inheritance for gene: SPAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5033 | MMP21 | Zornitza Stark Mode of inheritance for gene: MMP21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5030 | DNAAF1 | Zornitza Stark Mode of inheritance for gene: DNAAF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5027 | LRRC6 | Zornitza Stark Mode of inheritance for gene: LRRC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5024 | GAS8 | Zornitza Stark Mode of inheritance for gene: GAS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5021 | DNAI2 | Zornitza Stark Mode of inheritance for gene: DNAI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5018 | DNAI1 | Zornitza Stark Mode of inheritance for gene: DNAI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5014 | DNAAF5 | Zornitza Stark Mode of inheritance for gene: DNAAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5011 | DNAAF3 | Zornitza Stark Mode of inheritance for gene: DNAAF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5008 | RAB27A | Zornitza Stark Mode of inheritance for gene: RAB27A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5005 | DNAAF2 | Zornitza Stark Mode of inheritance for gene: DNAAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5003 | PPP1R13L |
Zornitza Stark gene: PPP1R13L was added gene: PPP1R13L was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PPP1R13L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP1R13L were set to 32666529; 28864777 Phenotypes for gene: PPP1R13L were set to Dilated cardiomyopathy, onset in infancy Review for gene: PPP1R13L was set to GREEN Added comment: Four families reported in PMID 28864777, but same homozygous variant, identity by descent. Five unrelated families reported in PMID 32666529. Severe progressive DCM with onset in infancy. Sources: Expert list |
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| Mendeliome v0.5000 | CCNO | Zornitza Stark Mode of inheritance for gene: CCNO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4998 | CSNK1G1 |
Zornitza Stark gene: CSNK1G1 was added gene: CSNK1G1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CSNK1G1 were set to 33009664 Phenotypes for gene: CSNK1G1 were set to Global developmental delay; Intellectual disability; Autism; Seizures Review for gene: CSNK1G1 was set to GREEN Added comment: Borderline Green/Amber rating. Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883). Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress). CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited). One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn]. Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD. There were no variant studies performed. The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies). Sources: Literature |
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| Mendeliome v0.4995 | LMNB2 | Zornitza Stark Mode of inheritance for gene: LMNB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4989 | CCDC40 | Zornitza Stark Mode of inheritance for gene: CCDC40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4986 | CCDC39 | Zornitza Stark Mode of inheritance for gene: CCDC39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4983 | CCDC151 | Zornitza Stark Mode of inheritance for gene: CCDC151 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4980 | CCDC114 | Zornitza Stark Mode of inheritance for gene: CCDC114 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4977 | CCDC103 | Zornitza Stark Mode of inheritance for gene: CCDC103 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4976 | CCDC103 | Zornitza Stark Tag founder tag was added to gene: CCDC103. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4974 | GARS | Zornitza Stark Mode of inheritance for gene: GARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4973 | GARS | Zornitza Stark Tag new gene name tag was added to gene: GARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4971 | SELENON | Zornitza Stark Mode of inheritance for gene: SELENON was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4969 | TNNT1 | Zornitza Stark Mode of inheritance for gene: TNNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4966 | TNNT3 | Zornitza Stark Mode of pathogenicity for gene: TNNT3 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4965 | TNNT3 | Zornitza Stark Mode of inheritance for gene: TNNT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4964 | STAC3 | Zornitza Stark Tag founder tag was added to gene: STAC3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4962 | STAC3 | Zornitza Stark Mode of inheritance for gene: STAC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4959 | SPEG | Zornitza Stark Mode of inheritance for gene: SPEG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4956 | TPM3 | Zornitza Stark Mode of pathogenicity for gene: TPM3 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4955 | TPM3 | Zornitza Stark Mode of inheritance for gene: TPM3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4954 | MICU1 | Zornitza Stark Tag founder tag was added to gene: MICU1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4952 | MICU1 | Zornitza Stark Mode of inheritance for gene: MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4949 | LMOD3 | Zornitza Stark Mode of inheritance for gene: LMOD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4945 | MYH2 | Zornitza Stark Mode of inheritance for gene: MYH2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4942 | KLHL41 | Zornitza Stark Mode of inheritance for gene: KLHL41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4941 | KLHL40 | Zornitza Stark Tag founder tag was added to gene: KLHL40. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4939 | KLHL40 | Zornitza Stark Mode of inheritance for gene: KLHL40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4936 | MYO18B | Zornitza Stark Mode of inheritance for gene: MYO18B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4933 | MEGF10 | Zornitza Stark Mode of inheritance for gene: MEGF10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4928 | WDPCP | Zornitza Stark Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4924 | TUBGCP4 | Zornitza Stark Mode of inheritance for gene: TUBGCP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4921 | DYNC2LI1 | Zornitza Stark Mode of inheritance for gene: DYNC2LI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4917 | TRAPPC9 | Zornitza Stark Tag SV/CNV tag was added to gene: TRAPPC9. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4914 | FKBP14 | Zornitza Stark Mode of inheritance for gene: FKBP14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4911 | EPG5 | Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4908 | LMX1B | Zornitza Stark Mode of inheritance for gene: LMX1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4905 | SEMA4A | Zornitza Stark Mode of inheritance for gene: SEMA4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4901 | JPH2 | Zornitza Stark Mode of inheritance for gene: JPH2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4899 | RGR | Zornitza Stark Tag disputed tag was added to gene: RGR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4897 | RGR | Zornitza Stark Mode of inheritance for gene: RGR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4895 | RDH11 |
Zornitza Stark gene: RDH11 was added gene: RDH11 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RDH11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RDH11 were set to 24916380; 15634683; 30731079; 18326732 Phenotypes for gene: RDH11 were set to Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108 Review for gene: RDH11 was set to RED Added comment: Single family reported with compound heterozygous LOF variants segregating with disease in three siblings. Some functional data, but note mouse KO did not have eye phenotype. Sources: Expert list |
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| Mendeliome v0.4892 | PRDM13 |
Zornitza Stark Tag SV/CNV tag was added to gene: PRDM13. Tag 5'UTR tag was added to gene: PRDM13. |
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| Mendeliome v0.4892 | GPC6 | Zornitza Stark Tag SV/CNV tag was added to gene: GPC6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4890 | GPC6 | Zornitza Stark Mode of inheritance for gene: GPC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4887 | SPATA7 | Zornitza Stark Mode of inheritance for gene: SPATA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4886 | KIRREL3 |
Zornitza Stark gene: KIRREL3 was added gene: KIRREL3 was added to Mendeliome. Sources: Expert list refuted tags were added to gene: KIRREL3. Mode of inheritance for gene: KIRREL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIRREL3 were set to 19012874 Phenotypes for gene: KIRREL3 were set to Intellectual disability Review for gene: KIRREL3 was set to RED Added comment: Variants associated with ID have now been re-classified based on population frequency. Sources: Expert list |
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| Mendeliome v0.4883 | NEUROD1 | Zornitza Stark Mode of inheritance for gene: NEUROD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4882 | DNAAF4 |
Zornitza Stark Tag SV/CNV tag was added to gene: DNAAF4. Tag founder tag was added to gene: DNAAF4. |
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| Mendeliome v0.4880 | DNAAF4 | Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4880 | DNAAF4 | Zornitza Stark Mode of inheritance for gene: DNAAF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4876 | GZF1 | Zornitza Stark Mode of inheritance for gene: GZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4874 | ITFG2 |
Zornitza Stark gene: ITFG2 was added gene: ITFG2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z Phenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia Review for gene: ITFG2 was set to AMBER Added comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51). Cheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS. Evaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)]. As discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306). Rated Amber as Cheema et al report on diagnostic outcomes and multiple candidate genes as part of a heterogenous cohort and details are therefore limited. Sources: Literature |
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| Mendeliome v0.4872 | SHMT2 |
Zornitza Stark gene: SHMT2 was added gene: SHMT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SHMT2 were set to 33015733 Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly Review for gene: SHMT2 was set to GREEN Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants. All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs. Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF. Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes. While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction. Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect. The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). Sources: Literature |
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| Mendeliome v0.4869 | DHX38 | Zornitza Stark Mode of inheritance for gene: DHX38 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4867 | CCT2 |
Zornitza Stark gene: CCT2 was added gene: CCT2 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: CCT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCT2 were set to 27645772; 29450543 Phenotypes for gene: CCT2 were set to Leber's congenital amaurosis Review for gene: CCT2 was set to RED Added comment: Single family reported with compound het missense variants, functional data, including animal model. Sources: NHS GMS |
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| Mendeliome v0.4864 | CA4 | Zornitza Stark Mode of inheritance for gene: CA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4862 | VPS41 |
Zornitza Stark gene: VPS41 was added gene: VPS41 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS41 were set to 32808683 Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability Review for gene: VPS41 was set to RED Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders. Sources: Literature |
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| Mendeliome v0.4860 | VPS16 |
Zornitza Stark gene: VPS16 was added gene: VPS16 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: VPS16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VPS16 were set to 32808683 Phenotypes for gene: VPS16 were set to Dystonia Added comment: 18 individuals reported with high-impact variants in VPS16 and a progressive early onset dystonia (median age 12 years, range 3–50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Progressive generalization ensued, although most remained ambulant, and only a minority (16%) lost the ability to walk in adulthood. Additional clinical features of mild to moderate intellectual disability and neuropsychiatric symptoms were present in approximately one‐third. In 4 individuals, magnetic resonance imaging (MRI) showed bilateral and symmetrical hypointensity of the globi pallidi and sometimes also the midbrain and dentate nuclei, suggestive of iron deposition. Mild generalized cerebral atrophy was also apparent in 4 individuals. Sources: Literature |
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| Mendeliome v0.4859 | KRIT1 | Zornitza Stark Tag founder tag was added to gene: KRIT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4857 | KRIT1 | Zornitza Stark Mode of inheritance for gene: KRIT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4854 | SH3TC2 | Zornitza Stark Mode of inheritance for gene: SH3TC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4853 | ABCC6 | Zornitza Stark Tag SV/CNV tag was added to gene: ABCC6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4851 | CAPN3 | Zornitza Stark Mode of inheritance for gene: CAPN3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4848 | SLC6A5 | Zornitza Stark Mode of pathogenicity for gene: SLC6A5 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4847 | SLC6A5 | Zornitza Stark Mode of inheritance for gene: SLC6A5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4844 | ARX | Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4842 | MCM2 |
Zornitza Stark gene: MCM2 was added gene: MCM2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: MCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MCM2 were set to 26196677 Phenotypes for gene: MCM2 were set to Deafness, autosomal dominant 70, MIM# 616968 Review for gene: MCM2 was set to RED Added comment: One family, expression studies. Sources: Expert Review |
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| Mendeliome v0.4841 | ATP1A4 |
Zornitza Stark gene: ATP1A4 was added gene: ATP1A4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATP1A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP1A4 were set to 32549268 Phenotypes for gene: ATP1A4 were set to Hemiplegic migraine Review for gene: ATP1A4 was set to RED Added comment: Single family reported where missense variant segregated with hemiplegic migraine in four affected individuals. Sources: Literature |
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| Mendeliome v0.4838 | BSND | Zornitza Stark Mode of inheritance for gene: BSND was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4835 | LTBP2 | Zornitza Stark Mode of inheritance for gene: LTBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4827 | IL11RA | Zornitza Stark Mode of inheritance for gene: IL11RA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4823 | EFNB1 | Zornitza Stark Mode of inheritance for gene: EFNB1 was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4821 | AGAP1 |
Zornitza Stark gene: AGAP1 was added gene: AGAP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AGAP1 were set to 31700678; 25666757; 30472483 Phenotypes for gene: AGAP1 were set to Cerebral palsy Review for gene: AGAP1 was set to AMBER Added comment: Two individuals reported with de novo variants in this gene and a CP phenotype. Rare variants over-represented in a case-control study. Supportive zebrafish model. Another individual with a deletion (+1 other gene) reported with ID and autism. Sources: Literature |
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| Mendeliome v0.4818 | SMN1 | Zornitza Stark Mode of inheritance for gene: SMN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4817 | SMN1 | Zornitza Stark Tag SV/CNV tag was added to gene: SMN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4815 | BUB1B | Zornitza Stark Mode of inheritance for gene: BUB1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4812 | ROM1 | Zornitza Stark Mode of inheritance for gene: ROM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4809 | FOXC1 | Zornitza Stark Mode of inheritance for gene: FOXC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4805 | ACER3 | Zornitza Stark Mode of inheritance for gene: ACER3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4799 | NUAK2 | Zornitza Stark Mode of inheritance for gene: NUAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4794 | AP1S1 | Zornitza Stark Mode of inheritance for gene: AP1S1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4789 | THOC1 |
Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested. Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis. Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested. Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the hypomorphic thoc1 in mouse induced hair cell apoptosis. Sources: Literature |
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| Mendeliome v0.4789 | GOLGA3 |
Elena Savva gene: GOLGA3 was added gene: GOLGA3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GOLGA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GOLGA3 were set to PMID: 23495255 Phenotypes for gene: GOLGA3 were set to Primary ciliary dyskinesia Review for gene: GOLGA3 was set to RED Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2 Two siblings with a homozygous missense and PCD PMID: 23495255; null mice have failed spermatogenesis Sources: Literature |
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| Mendeliome v0.4788 | AKNA |
Elena Savva gene: AKNA was added gene: AKNA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AKNA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AKNA were set to PMID: 21606955 Phenotypes for gene: AKNA were set to Primary ciliary dyskinesia Review for gene: AKNA was set to RED Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2 Two siblings with homozygous PTCs with PCD. Carrier parents and mutation negative siblings (5) was normal. PMID: 21606955: Null mice have neonatal death with systemic inflammation and alveolar loss Sources: Literature |
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| Mendeliome v0.4786 | THOC1 |
Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested. Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis. Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested. Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis. Sources: Literature |
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| Mendeliome v0.4784 | RNPC3 |
Zornitza Stark gene: RNPC3 was added gene: RNPC3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNPC3 were set to 29866761; 32462814 Phenotypes for gene: RNPC3 were set to Growth hormone deficiency Review for gene: RNPC3 was set to AMBER Added comment: Two families reported. PMID 29866761: isolated growth deficiency and pituitary hypoplasia. PMID 32462814: growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. Full spectrum of phenotype unclear at present. Sources: Literature |
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| Mendeliome v0.4783 | THOC1 |
Melanie Marty changed review comment from: Missense variant identified and segregated with adulthood-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested. Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis. Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested. Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis. Sources: Literature |
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| Mendeliome v0.4783 | PRICKLE3 |
Teresa Zhao gene: PRICKLE3 was added gene: PRICKLE3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PRICKLE3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: PRICKLE3 were set to 32516135 Phenotypes for gene: PRICKLE3 were set to Leber’s hereditary optic neuropathy MIM#535000 Review for gene: PRICKLE3 was set to AMBER Added comment: Reported as X-linked LHON modifier (c.157C>T, p.Arg53Trp) in PRICKLE3 in 3 Chinese families. All affected individuals carried both ND4 11778G>A and p.Arg53Trp mutations, while subjects bearing only a single mutation exhibited normal vision. Defective assembly, stability, and function of ATP synthase observed using Lymphoblastoid cell lines from one of the families. This finding indicated that the p.Arg53Trp mutation acted in synergy with the m.11778G>A mutation and deteriorated mitochondrial dysfunctions necessary for the expression of LHON. Prickle3-deficient mice exhibited pronounced ATPase deficiencies. Sources: Literature |
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| Mendeliome v0.4783 | NUAK2 |
Seb Lunke gene: NUAK2 was added gene: NUAK2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NUAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NUAK2 were set to 32845958 Phenotypes for gene: NUAK2 were set to ANENCEPHALY (OMIM#206500) Review for gene: NUAK2 was set to AMBER Added comment: Novel gene described in single consanguineous family with three FDIU and extensive anencephaly. Hom inframe del affecting functional kinase domain, parents confirmed carriers. Good functional data showing loss of enzyme function and mouse model with 40% anencephaly after knock-out. Sources: Literature |
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| Mendeliome v0.4782 | THOC1 |
Melanie Marty gene: THOC1 was added gene: THOC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: THOC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: THOC1 were set to 32776944 Phenotypes for gene: THOC1 were set to Nonsyndromic hearing loss Review for gene: THOC1 was set to AMBER Added comment: Missense variant identified and segregated with adulthood-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested. Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis. Sources: Literature |
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| Mendeliome v0.4781 | MBTPS1 |
Zornitza Stark gene: MBTPS1 was added gene: MBTPS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013 Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia Review for gene: MBTPS1 was set to GREEN Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature. Sources: Literature |
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| Mendeliome v0.4780 | GBF1 |
Paul De Fazio gene: GBF1 was added gene: GBF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GBF1 were set to 32937143 Phenotypes for gene: GBF1 were set to Axonal Neuropathy Review for gene: GBF1 was set to GREEN gene: GBF1 was marked as current diagnostic Added comment: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo). Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals. Sources: Literature |
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| Mendeliome v0.4780 | ALS2 |
Ain Roesley gene: ALS2 was added gene: ALS2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALS2 were set to 32214227 Phenotypes for gene: ALS2 were set to Tetraparesis with affection of upper and lower motor neuron Penetrance for gene: ALS2 were set to unknown Review for gene: ALS2 was set to RED Added comment: In a cohort of Palestinian and Israeli Arabs with neurological disorders, a family with 2 affecteds were homozygous for a nonsense variant. Authors classified as likely path by ACMG guidelines Sources: Literature |
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| Mendeliome v0.4778 | QRICH1 | Zornitza Stark Mode of inheritance for gene: QRICH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4775 | GREB1L | Zornitza Stark Mode of inheritance for gene: GREB1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4774 | IL1RAP |
Zornitza Stark gene: IL1RAP was added gene: IL1RAP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IL1RAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL1RAP were set to 31954058 Phenotypes for gene: IL1RAP were set to Steroid-sensitive nephrotic syndrome Review for gene: IL1RAP was set to RED Added comment: A pair of siblings with compound heterozygous variants in this gene and steroid-sensitive nephrotic syndrome. Functional effect of variants demonstrated but mouse model does not have proteinuria. Sources: Literature |
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| Mendeliome v0.4771 | NEMF | Zornitza Stark Mode of inheritance for gene: NEMF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4767 | HOMER2 | Zornitza Stark Mode of inheritance for gene: HOMER2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4764 | TPRN | Zornitza Stark Mode of inheritance for gene: TPRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4761 | TMC1 | Zornitza Stark Mode of inheritance for gene: TMC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4759 | TMIE | Zornitza Stark Mode of inheritance for gene: TMIE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4755 | TRIOBP | Zornitza Stark Mode of inheritance for gene: TRIOBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4752 | STRC | Zornitza Stark Mode of inheritance for gene: STRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4749 | SETD1A |
Zornitza Stark gene: SETD1A was added gene: SETD1A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SETD1A were set to 31197650; 32346159 Phenotypes for gene: SETD1A were set to Epilepsy, early-onset, with or without developmental delay, MIM# 618832 Review for gene: SETD1A was set to GREEN Added comment: 19 unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype, primarily manifesting and ID and seizures. LOF mechanism supported by functional data. Three mouse models. SNPs in this gene have also been associated with risk of developing schizophrenia. Sources: Literature |
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| Mendeliome v0.4747 | HPDL |
Zornitza Stark commented on gene: HPDL: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%). Frequently observed clinical findings included chronic progression of neurological signs (n = 16/17, 94%), motor developmental delay (n = 12/17, 71%), intellectual impairment (n = 11/17, 65%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%). Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%). Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one. |
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| Mendeliome v0.4743 | SCN1A | Zornitza Stark edited their review of gene: SCN1A: Added comment: Note we have reported the association with AMC previously in PMID 29543227 (Supplementary info) in an infant presenting with AMC and severe EE, and de novo p.(Ile1347Asn) variant which at the time was thought to only partially explain the phenotype, but in light of this new report, likely fully explains the phenotype. Given the presence of severe seizure disorder in the two infants who were phenotyped in the newborn period, this likely represents the severe end of the spectrum of SCN1A-related disorders rather than a distinct association.; Changed phenotypes: Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208, Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome, Febrile seizures, Arthrogryposis multiplex congenita | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4740 | SIX1 | Zornitza Stark Mode of inheritance for gene: SIX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4737 | PTPRQ | Zornitza Stark Mode of inheritance for gene: PTPRQ was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4734 | POU4F3 | Zornitza Stark Mode of inheritance for gene: POU4F3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4731 | KPTN | Zornitza Stark Mode of inheritance for gene: KPTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4729 | NPHS1 | Zornitza Stark Mode of inheritance for gene: NPHS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4726 | TTI2 | Zornitza Stark Mode of inheritance for gene: TTI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4724 | IGSF10 |
Bryony Thompson gene: IGSF10 was added gene: IGSF10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IGSF10 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: IGSF10 were set to 27137492; 31042289 Phenotypes for gene: IGSF10 were set to delayed puberty; hypogonadotropic hypogonadism; primary ovary insufficiency Review for gene: IGSF10 was set to AMBER Added comment: PMID: 27137492 - 4 Finnish families segregating p.Glu161Lys, but Finnish MAF in ExAC is 2%. Another six additional families with a possible missense, but variants are seen in ExAC suggesting incomplete penetrance. Supporting in vitro functional assays and zebrafish model. PMID: 31042289 - 2 unrelated consanguineous families with homozygous variants and family with a heterozygous frameshift and apparent incomplete penetrance. Sources: Literature |
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| Mendeliome v0.4721 | PFN1 | Zornitza Stark Mode of inheritance for gene: PFN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4718 | PCDH15 | Zornitza Stark Mode of inheritance for gene: PCDH15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4715 | WHRN | Zornitza Stark Mode of inheritance for gene: WHRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4712 | OTOGL | Zornitza Stark Mode of inheritance for gene: OTOGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4709 | RDX | Zornitza Stark Mode of inheritance for gene: RDX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4706 | OTOA | Zornitza Stark Mode of inheritance for gene: OTOA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4703 | MYO7A | Zornitza Stark Mode of inheritance for gene: MYO7A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4700 | SMPX | Zornitza Stark Mode of inheritance for gene: SMPX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4697 | MYO6 | Zornitza Stark Mode of inheritance for gene: MYO6 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4694 | MYO15A | Zornitza Stark Mode of inheritance for gene: MYO15A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4691 | MYH9 | Zornitza Stark Mode of inheritance for gene: MYH9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4688 | MARVELD2 | Zornitza Stark Mode of inheritance for gene: MARVELD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4683 | LRTOMT | Zornitza Stark Mode of inheritance for gene: LRTOMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4680 | LHFPL5 | Zornitza Stark Mode of inheritance for gene: LHFPL5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4677 | GYS1 | Zornitza Stark Mode of inheritance for gene: GYS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4673 | PIGT | Zornitza Stark Mode of inheritance for gene: PIGT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4670 | ALG13 | Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4668 | BLOC1S5 |
Zornitza Stark gene: BLOC1S5 was added gene: BLOC1S5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BLOC1S5 were set to 32565547 Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome Review for gene: BLOC1S5 was set to GREEN Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2). Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively. Sources: Literature |
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| Mendeliome v0.4665 | FOXL2 | Zornitza Stark Mode of inheritance for gene: FOXL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4662 | ILDR1 | Zornitza Stark Mode of inheritance for gene: ILDR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4659 | HOXA2 | Zornitza Stark Mode of inheritance for gene: HOXA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4656 | GRXCR1 | Zornitza Stark Mode of inheritance for gene: GRXCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4653 | GPSM2 | Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4650 | GIPC3 | Zornitza Stark Mode of inheritance for gene: GIPC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4645 | CNOT1 | Zornitza Stark Mode of inheritance for gene: CNOT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4641 | GATA3 | Zornitza Stark Mode of inheritance for gene: GATA3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4637 | EYA4 | Zornitza Stark Mode of inheritance for gene: EYA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4634 | ESPN | Zornitza Stark Mode of inheritance for gene: ESPN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4631 | DFNB59 | Zornitza Stark Mode of inheritance for gene: DFNB59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4628 | DFNA5 | Zornitza Stark Mode of inheritance for gene: DFNA5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4627 | DFNA5 | Zornitza Stark Tag new gene name tag was added to gene: DFNA5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4626 | PRIMPOL | Zornitza Stark Tag disputed tag was added to gene: PRIMPOL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4622 | COL4A5 | Zornitza Stark Mode of inheritance for gene: COL4A5 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4619 | COCH | Zornitza Stark Mode of inheritance for gene: COCH was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4616 | CLRN1 | Zornitza Stark Mode of inheritance for gene: CLRN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4613 | CLPP | Zornitza Stark Mode of inheritance for gene: CLPP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4610 | CLDN14 | Zornitza Stark Mode of inheritance for gene: CLDN14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4607 | CIB2 | Zornitza Stark Mode of inheritance for gene: CIB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4604 | GCM2 | Zornitza Stark Mode of pathogenicity for gene: GCM2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4603 | GCM2 | Zornitza Stark Mode of inheritance for gene: GCM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4600 | SECISBP2 | Zornitza Stark Mode of inheritance for gene: SECISBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4597 | UBA1 | Zornitza Stark Mode of inheritance for gene: UBA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4594 | TRIP4 | Zornitza Stark Mode of inheritance for gene: TRIP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4591 | EXOSC9 | Zornitza Stark Mode of inheritance for gene: EXOSC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4588 | SLC7A14 | Zornitza Stark Mode of inheritance for gene: SLC7A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4586 | SLC7A14 | Zornitza Stark Tag disputed tag was added to gene: SLC7A14. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4584 | ATP6V1B1 | Zornitza Stark Mode of inheritance for gene: ATP6V1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4579 | ALB | Zornitza Stark Mode of inheritance for gene: ALB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4576 | TREM2 | Zornitza Stark Mode of inheritance for gene: TREM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4573 | SPG21 | Zornitza Stark Mode of inheritance for gene: SPG21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4572 | SPG21 | Zornitza Stark Tag new gene name tag was added to gene: SPG21. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4570 | LMX1A | Zornitza Stark Mode of inheritance for gene: LMX1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4568 | RPS20 |
Bryony Thompson gene: RPS20 was added gene: RPS20 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RPS20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPS20 were set to 32790018 Phenotypes for gene: RPS20 were set to Diamond Blackfan anaemia Mode of pathogenicity for gene: RPS20 was set to Other Review for gene: RPS20 was set to AMBER Added comment: Two unrelated cases where a de novo variant involving Ile84 (Ile84Ser and Ile84Asn), and reduce the RPS20 protein level in patient cells. Yeast models with mutation of the cognate residue resulted in defects in growth, ribosome biogenesis, and polysome formation. Loss of function may not be the mechanism of disease, because loss of function variants appear to be exclusively associated with familial colorectal cancer without the DBA phenotype. Sources: Literature |
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| Mendeliome v0.4564 | SPAST | Zornitza Stark Mode of inheritance for gene: SPAST was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4561 | TRRAP | Zornitza Stark Mode of inheritance for gene: TRRAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4558 | UPF3B | Zornitza Stark Mode of inheritance for gene: UPF3B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4555 | XPR1 | Zornitza Stark Mode of inheritance for gene: XPR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4552 | VPS13C | Zornitza Stark Mode of inheritance for gene: VPS13C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4549 | KIAA1161 | Zornitza Stark Mode of inheritance for gene: KIAA1161 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4548 | KIAA1161 | Zornitza Stark Tag new gene name tag was added to gene: KIAA1161. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4548 | KIAA1161 | Zornitza Stark edited their review of gene: KIAA1161: Added comment: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16). HGNC approved name is MYORG.; Changed publications: 30656188, 30649222, 30460687, 29910000, 31951047; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4546 | ALG14 | Zornitza Stark Mode of inheritance for gene: ALG14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4543 | TCF12 | Zornitza Stark Mode of inheritance for gene: TCF12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4540 | RP1L1 | Zornitza Stark Mode of inheritance for gene: RP1L1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4537 | CYP11B2 | Zornitza Stark Mode of inheritance for gene: CYP11B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4534 | HPS5 | Zornitza Stark Mode of inheritance for gene: HPS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4529 | IBA57 | Zornitza Stark Mode of inheritance for gene: IBA57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4523 | PAX7 | Zornitza Stark Mode of inheritance for gene: PAX7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4520 | SLC12A2 |
Zornitza Stark edited their review of gene: SLC12A2: Added comment: Monoallelic : DD/ID was a feature in >= 6 individuals with monoallelic de novo SLC12A2. An individual with an exon 22 truncating variant was reported to have normal milestones and cognitive function. Exon 21 variants have been described in individuals with rather isolated hearing impairment (possibly some associated motor delay, but normal cognition). Hearing impairment was also reported in 2/6 patients with variants in other exons (1 missense / 1 frameshift). Biallelic : DD/ID was reported in at least 3 individuals in literature. Hearing impairment has been reported on 2 occasions (although this was not probably evaluated in all subjects). --- Monoallelic SLC12A2 mutations : ► Individuals with de novo mutations and developmental disorder were first identified by the DDD study (2017 - PMID: 28135719). 5 of them have been reported in detail by McNeill et al (below). ► McNeill et al (2020 - PMID: 32658972) report on 6 individuals with neurodevelopmental disorder due to de novo SLC12A2 mutation. All presented DD or ID ranging from mild to severe. ASD was reported in 3/6. Sensorineural hearing loss was a feature in 2/6 with the remaining having normal formal evaluations. Brain, cardiac and/or additional malformations were reported in a single individual. Following non-diagnostic prior work-up (CMA, FMR1 or other investigations) trio exome sequencing revealed missense (4/6) or truncating variants (2/6). Three additional individuals (incl. a father and his son) with missense variants in exon 21 (NM_001046.3 / p.Glu979Lys and p.Glu980Lys) presented with bilateral sensorineural hearing loss. Speech and/or motor delay reported in these cases were attributed to the hearing impairment/vestibular arreflexia (cognitive abilities not tested). SLC12A2 encodes sodium-potassium-chloride transporter 1 (also NKCC1). The GTEx project has identified 8 isoforms. In brain both exon 21-containing/deleted isoforms are expressed (cited Morita et al 2014 - PMID: 24695712). As the authors discuss, RNA-seq of the developing mouse cochlea suggests that the exon 21 containing isoform is the single transcript expressed. Evidence from RNA-seq data (BrainSpan project) and literature suggests that the significant amounts of exon 21 lacking isoforms in fetal brain compensate for the deleterious effects of exon 21 variants and explain the lack of NDD in relevant patients. Slc12a2 (NKCC1) null mouse model has demonstrated that the transporter plays a role in accumulation of the potassium rich endolymph in the inner ear, with NKCC1 absence causing sensorineural deafness and imbalance. Slc12a2 display cochlear malformations, loss of hair cells and hearing impairment (cited Delpire et al 1999 - PMID: 10369265). The brain phenotype has not been studied extensively, although loss of Slc12a2 has been shown to inhibit neurogenesis (cited: Magalhães and Rivera et al. - PMID: 27582690). Slc12a2 null zebrafish display a collapse of the otic vesicle and reduced endolymph (Abbas and Whitfield, 2009 - PMID: 19633174) relevant to the human hearing disorder. In vitro assessment of NKCC1 ion transporter function in Xenopus laevis, supported the deleterious effect of the identified variants (significant reduction in K+ influx). Using available single cell RNA-seq data the authors further demonstrated that SLC12A2 expressing cells display transcriptomic profiles reflective of active neurogenesis. ► Delpire et al (2016 - PMID: 27900370 - not reviewed in detail) described a 13 y.o. girl harboring a de novo 11-bp deletion in SLC12A2 exon 22. This individual reached developmental milestones on time and had a NORMAL cognitive function. Hearing was seemingly normal. Features included orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency and multiorgan failure incl. gut and bladder. Exome in the proband, parents and 3 unaffected sibs suggested SLC12A2 as the only candidate for her phenotype. Functional analyses in Xenopus laevis oocytes suggested that a non functional transporter was expressed and trafficked to the membrane as the wt. Detection of the truncated protein at higher molecular sizes suggested either enhanced dimerization or misfolded aggregate. There was no dominant-negative effect of mutant NKCC1. In patient fibroblasts a reduced total and NKCC1-mediated K+ influx. ► Mutai et al (2020 - PMID: 32294086) report on several individuals from 4 families, harboring variants within exon 21 or - in one case - at it's 3' splice-site (leading to skipping oe this exon at the mRNA level). All subjects were investigated for severe/profound hearing loss (in line with the role of exon 21-included isoforms in cochlea. The variant segregated with hearing impairment in 3 generations of a family while in all other subjects the variant had occured as de novo event. Despite motor delays (e.g. the subject from fam2 could not hold head or sit at the age of 10m / the proband in Fam3 was able to hold his head and walk at 6 and 20 m respectively) behavior and cognition were commented to be within normal range. ----- Biallelic SLC12A2 mutations: ► Anazi et al (2017 - PMID: 29288388) briefly reported on a 3 y.o. boy (17DG0776) with central hypotonia, neonatal respiratory distress, failure to thrive, global DD and microcephaly and a skeletal survey suggestive of osteopenia. After non-diagnostic prior investigations (CMA revealing a 1p duplication classified as VUS, extensive metabolic workup), WES revealed a homozygous SLC12A2 splicing variant [NM_001046.2:c.2617-2A>G]. ► Macnamara et al (2019 - PMID: 30740830) described a 5.5 y.o. male with sensorineural hearing loss, profound delays in all developmental areas among several other features (choanal atresia, failure to thrive, respiratory problems, absent sweat and tear production or salivation, GI abnormalities). Genetic testing for several disorders considered (cystic fibrosis, spinal muscular atrophy, sequencing and del/dup analysis of mtDNA) was normal. CMA revealed paternal uniparental isodisomy for chr. 5 and WGS a homozygous 22kb deletion in SLC12A2. This was followed by confirmation of homozygosity in the proband, heterozygosity of the unaffected father, delineation of breakpoints (chr5:127441491-127471419). mRNA studies in patient fibroblasts confirmed deletion of ex2-7, splicing of ex1 directly to ex8 and introduction of a premature stop codon in ex9. qRT-PCR confirmed that mRNA is likely subjected to NMD (expression ~80% of control). Western blot confirmed absence of the protein in the patient's fibroblasts. Again mouse models are thought to recapitulate the hearing defect but also the deficient saliva production (cited Evans et al 2000 - PMID: 10831596). Again the authors speculate a role of SLC12A2 in brain development based on evidence from murine models (migration, dendritic growth, increse in neuron density through regulation of GABAergic signalling (Young et al 2012 - PMID: 23015452). Hypotheses are also made on a regulatory relationship between NKCC1 and CFTR based on mRNA data from the ko mouse model. ► Stödberg et al (2020 - PMID: 32754646) reported 2 sibs with a complex neurodevelopmental disorder due to compound heterozygosity for a frameshift SLC12A2 variant and a splicing one (NM_001046:c.1431delT and c.2006-1G>A). Both presented hypotonia, neonatal S. aureus parotitis and respiratory problems (incl. apneas). While the older sib died at the age of 22 days, the younger one had persistent respiratory issues incl. a dry respiratory mucosa motivating metabolic, immunology investigations and testing for CF. She displayed microcephaly (OFC -2.5 SD, H was also -3.5SD), severe intellectual disability. MRI was suggestive of white matter and basal ganglia abnormalities. Other features incl. hearing impairment, and lack of tears,saliva and sweat, constipation and intestinal malrotation. There was facial dysmorphism. The variants were the only retained following WGS of the 2 affected sisters, parents and an unaffected brother. The splicing variant was shown to result in skipping of exon 13, while the indel in NMD. Again the authors discuss that the deficient saliva production, impaired hearing and GI problems are recapitulated in the mouse model (several refs provided).; Changed rating: GREEN; Changed publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Changed phenotypes: Kilquist syndrome, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.4518 | VPS37A | Zornitza Stark Mode of inheritance for gene: VPS37A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4514 | TECPR2 | Zornitza Stark Mode of inheritance for gene: TECPR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4511 | SMOC2 | Zornitza Stark Mode of inheritance for gene: SMOC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4508 | MAG | Zornitza Stark Mode of inheritance for gene: MAG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4507 | DSTYK | Zornitza Stark Tag SV/CNV tag was added to gene: DSTYK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4505 | DSTYK | Zornitza Stark Mode of inheritance for gene: DSTYK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4503 | ZMYM2 |
Zornitza Stark gene: ZMYM2 was added gene: ZMYM2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZMYM2 were set to 32891193 Phenotypes for gene: ZMYM2 were set to Congenital anomalies of kidney and urinary tract; Neurodevelopmental disorder Review for gene: ZMYM2 was set to GREEN Added comment: Heterozygous pathogenic (pLoF) ZMYM2 variants have been reported in individuals with syndromic presentation including CAKUT (in several cases) and variable neurological manifestations among extra-renal features. -- Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants. Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly. 14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family. The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT. ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body). It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors. The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT). Sources: Literature |
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| Mendeliome v0.4501 | MTX2 |
Zornitza Stark gene: MTX2 was added gene: MTX2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTX2 were set to 32917887 Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification Review for gene: MTX2 was set to GREEN Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Sources: Literature |
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| Mendeliome v0.4500 | RREB1 |
Zornitza Stark gene: RREB1 was added gene: RREB1 was added to Mendeliome. Sources: Literature SV/CNV tags were added to gene: RREB1. Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RREB1 were set to 32938917 Phenotypes for gene: RREB1 were set to Noonan syndrome-like disorder Review for gene: RREB1 was set to RED Added comment: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes. In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association. Sources: Literature |
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| Mendeliome v0.4497 | NEMF |
Zornitza Stark gene: NEMF was added gene: NEMF was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEMF were set to 32934225 Phenotypes for gene: NEMF were set to Intellectual disability; neuropathy Review for gene: NEMF was set to GREEN Added comment: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration. Sources: Literature |
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| Mendeliome v0.4496 | FNIP1 |
Arina Puzriakova gene: FNIP1 was added gene: FNIP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FNIP1 were set to 32181500; 32905580 Phenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia Review for gene: FNIP1 was set to GREEN Added comment: - PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed. - PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway. Sources: Literature |
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| Mendeliome v0.4494 | TAOK1 | Zornitza Stark Mode of inheritance for gene: TAOK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4491 | CSF1R | Zornitza Stark Mode of pathogenicity for gene: CSF1R was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4490 | CSF1R | Zornitza Stark Mode of inheritance for gene: CSF1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4487 | L2HGDH | Zornitza Stark Mode of inheritance for gene: L2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4486 | LMNB1 | Zornitza Stark Mode of inheritance for gene: LMNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4485 | LMNB1 | Zornitza Stark Mode of pathogenicity for gene: LMNB1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4482 | LMNB1 | Zornitza Stark Tag SV/CNV tag was added to gene: LMNB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4480 | MAPK8 |
Arina Puzriakova gene: MAPK8 was added gene: MAPK8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAPK8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MAPK8 were set to 31784499 Phenotypes for gene: MAPK8 were set to Chronic mucocutaneous candidiasis; Connective tissue disorders Added comment: PMID: 31784499 (2020) - Three cases in a single family with chronic mucocutaneous candidiasis and a connective tissue disorder that clinically overlaps with hEDS. WES revealed a splice-site variant (c.311+1G>A) in the MAPK8 gene that segregated with the disorder. Includes supportive functional data using patient-derived fibroblasts, showing that the variant impairs IL-17A/F immunity and the development of Th17 cells. Sources: Literature |
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| Mendeliome v0.4480 | CTNNBL1 |
Arina Puzriakova gene: CTNNBL1 was added gene: CTNNBL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CTNNBL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTNNBL1 were set to 32484799 Phenotypes for gene: CTNNBL1 were set to Primary Immunodeficiency; Autoimmune Cytopenias; Common variable immunodeficiency Added comment: PMID: 32484799 (2020) - One patient with common variable immunodeficiency associated with autoimmune cytopenia (CVID+AIC), associated with a homozygous missense M466V variant in the CTNNBL1 gene. Functional studies showed that the variant impaired interaction with AID, in turn disrupting AID-mediated antibody diversification in activated B-cells. Sources: Literature |
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| Mendeliome v0.4477 | TNNI2 | Zornitza Stark Mode of pathogenicity for gene: TNNI2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4476 | TNNI2 | Zornitza Stark Mode of inheritance for gene: TNNI2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4471 | VPS11 | Zornitza Stark Mode of inheritance for gene: VPS11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4470 | VPS11 | Zornitza Stark Tag founder tag was added to gene: VPS11. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4468 | GGT1 | Zornitza Stark Mode of inheritance for gene: GGT1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4466 | GGT1 |
Elena Savva edited their review of gene: GGT1: Added comment: PMID: 29483667 - 1 family (2 sibs) w/ a homozygous 16.9kb deletion spanning part of the gene and no others. Carrier parents were normal. PMID: 23615310 - homozygous mutant mouse model have dwarfism, cataracts and coat colour abnormalities. Protein activity reduced to 4% of wildtype. Noted it was for use as a GGT deficiency model. PMID: 31520399 - 2 families with AD inheritance showing GGT1 deficiency but NO clinical symptoms. Authors call GGTemia a benign condition.; Changed publications: PMID: 29483667, 23615310, 31520399 |
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| Mendeliome v0.4464 | NAXE | Zornitza Stark Mode of inheritance for gene: NAXE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4461 | NAXD | Zornitza Stark Mode of inheritance for gene: NAXD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4458 | ISCA2 | Zornitza Stark Mode of inheritance for gene: ISCA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4455 | PRIMPOL | Zornitza Stark Mode of inheritance for gene: PRIMPOL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4452 | KCNN4 |
Zornitza Stark gene: KCNN4 was added gene: KCNN4 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: KCNN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNN4 were set to 26148990; 26198474; 26178367 Phenotypes for gene: KCNN4 were set to Dehydrated hereditary stomatocytosis 2, MIM# 616689 Review for gene: KCNN4 was set to GREEN Added comment: At least three families reported. Sources: Expert list |
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| Mendeliome v0.4450 | C15orf41 |
Zornitza Stark gene: C15orf41 was added gene: C15orf41 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: C15orf41 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C15orf41 were set to 23716552; 32293259; 31191338; 29885034 Phenotypes for gene: C15orf41 were set to Dyserythropoietic anemia, congenital, type Ib, MIM# 615631 Review for gene: C15orf41 was set to GREEN Added comment: At least 6 families reported, functional data. Sources: Expert list |
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| Mendeliome v0.4447 | XRCC2 | Zornitza Stark Mode of inheritance for gene: XRCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4443 | TSR2 | Zornitza Stark Mode of inheritance for gene: TSR2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4441 | SRP72 | Zornitza Stark Tag disputed tag was added to gene: SRP72. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4439 | SRP72 | Zornitza Stark Mode of inheritance for gene: SRP72 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4435 | SLC25A38 | Zornitza Stark Mode of inheritance for gene: SLC25A38 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4432 | SLC19A2 | Zornitza Stark Mode of inheritance for gene: SLC19A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4429 | SEC23B | Zornitza Stark Mode of inheritance for gene: SEC23B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4426 | RPS27 | Zornitza Stark Mode of inheritance for gene: RPS27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4422 | RPS17 | Zornitza Stark Mode of inheritance for gene: RPS17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4421 | RPL9 |
Zornitza Stark gene: RPL9 was added gene: RPL9 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RPL9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPL9 were set to 29114930; 20116044 Phenotypes for gene: RPL9 were set to Diamond Blackfan anaemia Review for gene: RPL9 was set to RED Added comment: PMID: 29114930, de novo splice site variant, c.-2+1G>C, functional impact of this variant is likely deleterious but not proven. Inherited missense variant reported in PMID 20116044, p.Arg125Ser is present in 31 hets in gnomad. Sources: Expert list |
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| Mendeliome v0.4418 | RPL31 | Zornitza Stark Mode of inheritance for gene: RPL31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4414 | PUS1 | Zornitza Stark Mode of inheritance for gene: PUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4410 | NHP2 | Zornitza Stark Mode of inheritance for gene: NHP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4407 | LIG4 | Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4404 | HOXA11 | Zornitza Stark Mode of inheritance for gene: HOXA11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4400 | TGM6 | Zornitza Stark Mode of inheritance for gene: TGM6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4398 | TGM6 | Zornitza Stark Tag refuted tag was added to gene: TGM6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4398 | SVBP | Zornitza Stark Tag founder tag was added to gene: SVBP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4396 | SQSTM1 | Zornitza Stark Mode of inheritance for gene: SQSTM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4395 | SQSTM1 | Zornitza Stark changed review comment from: Four unrelated families, presenting feature of this progressive neurological disorder was ataxia.; to: Nine individuals from four unrelated families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4393 | SLC25A46 | Zornitza Stark Mode of inheritance for gene: SLC25A46 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4390 | RORA | Zornitza Stark Mode of inheritance for gene: RORA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4387 | LARS2 | Zornitza Stark Mode of inheritance for gene: LARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4384 | LAMA1 | Zornitza Stark Mode of inheritance for gene: LAMA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4381 | KCNA2 | Zornitza Stark Mode of inheritance for gene: KCNA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4378 | HARS2 | Zornitza Stark Mode of inheritance for gene: HARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4375 | EBF3 | Zornitza Stark Mode of inheritance for gene: EBF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4372 | DOCK3 | Zornitza Stark Mode of inheritance for gene: DOCK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4369 | ATP8A2 | Zornitza Stark Mode of inheritance for gene: ATP8A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4368 | ADPRHL2 | Zornitza Stark Tag new gene name tag was added to gene: ADPRHL2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4366 | CNGB3 | Zornitza Stark Mode of inheritance for gene: CNGB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4363 | CNGA3 | Zornitza Stark Mode of inheritance for gene: CNGA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4360 | SPRED1 | Zornitza Stark Mode of inheritance for gene: SPRED1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4357 | SOS2 | Zornitza Stark Mode of pathogenicity for gene: SOS2 was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4353 | SHOC2 | Zornitza Stark Mode of pathogenicity for gene: SHOC2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4352 | SHOC2 | Zornitza Stark Mode of inheritance for gene: SHOC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4349 | RIT1 | Zornitza Stark Mode of pathogenicity for gene: RIT1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4348 | RIT1 | Zornitza Stark Mode of inheritance for gene: RIT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4345 | NRAS | Zornitza Stark Mode of pathogenicity for gene: NRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4344 | NRAS | Zornitza Stark Mode of inheritance for gene: NRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4341 | MAP2K2 | Zornitza Stark Mode of pathogenicity for gene: MAP2K2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4340 | MAP2K2 | Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4337 | MAP2K1 | Zornitza Stark Mode of pathogenicity for gene: MAP2K1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4336 | MAP2K1 | Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4333 | HRAS | Zornitza Stark Mode of pathogenicity for gene: HRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4332 | HRAS | Zornitza Stark Mode of inheritance for gene: HRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4329 | CBL | Zornitza Stark Mode of pathogenicity for gene: CBL was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4328 | CBL | Zornitza Stark Mode of inheritance for gene: CBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4325 | CSNK1D | Zornitza Stark Mode of inheritance for gene: CSNK1D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4321 | CACNA1E | Zornitza Stark Mode of inheritance for gene: CACNA1E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4318 | ATAD1 | Zornitza Stark Mode of inheritance for gene: ATAD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4315 | ADAT1 |
Zornitza Stark gene: ADAT1 was added gene: ADAT1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ADAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAT1 were set to 28180185; 29390050; 29659736 Phenotypes for gene: ADAT1 were set to Hyperekplexia 4, MIM#618011 Review for gene: ADAT1 was set to GREEN Added comment: Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Three unrelated families reported. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures. Sources: Expert list |
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| Mendeliome v0.4312 | OCA2 | Zornitza Stark Tag SV/CNV tag was added to gene: OCA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4310 | OCA2 | Zornitza Stark Mode of inheritance for gene: OCA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4309 | ZSWIM6 |
Zornitza Stark changed review comment from: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype. MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp; to: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X) identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype. MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp |
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| Mendeliome v0.4309 | ZSWIM6 |
Zornitza Stark changed review comment from: MIM #617865 A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype. MIM#603671: recurrent missense identified in 6 unrelated families, p.Arg1163Trp; to: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype. MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp |
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| Mendeliome v0.4306 | VPS13D | Zornitza Stark Mode of inheritance for gene: VPS13D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4304 | FARSA |
Zornitza Stark gene: FARSA was added gene: FARSA was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FARSA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FARSA were set to 31355908 Phenotypes for gene: FARSA were set to Rajab interstitial lung disease with brain calcifications 2, MIM# 619013 Review for gene: FARSA was set to RED Added comment: Autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts. Single affected individual reported, but FARSA interacts with FARSB, which causes a similar disorder. Sources: Expert list |
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| Mendeliome v0.4301 | SLC1A3 | Zornitza Stark Mode of inheritance for gene: SLC1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4299 | ANGPT2 |
Zornitza Stark gene: ANGPT2 was added gene: ANGPT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ANGPT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ANGPT2 were set to https://stm.sciencemag.org/content/12/560/eaax8013 Phenotypes for gene: ANGPT2 were set to Primary lymphoedema Review for gene: ANGPT2 was set to GREEN Added comment: Five unrelated individuals reported with primary lymphedema and variants in this gene, together with functional data. Sources: Literature |
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| Mendeliome v0.4296 | SLC20A2 | Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4293 | SLC16A2 | Zornitza Stark Mode of inheritance for gene: SLC16A2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4292 | TRIP13 | Zornitza Stark Tag founder tag was added to gene: TRIP13. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4290 | TRIP13 | Zornitza Stark Mode of inheritance for gene: TRIP13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4286 | NOBOX | Zornitza Stark Mode of inheritance for gene: NOBOX was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4283 | TET2 | Zornitza Stark Mode of inheritance for gene: TET2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4279 | TLR7 | Zornitza Stark Mode of inheritance for gene: TLR7 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4276 | EXOSC5 | Zornitza Stark Mode of inheritance for gene: EXOSC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4275 | EXOSC5 |
Arina Puzriakova changed review comment from: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXCOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient. Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively. A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5. - PMID: 29302074 (2019) - Three sibs with a homozygous EXCOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken.; to: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient. Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively. A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5. - PMID: 29302074 (2019) - Three sibs with a homozygous EXOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken. |
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| Mendeliome v0.4273 | SLC20A1 | Zornitza Stark Mode of inheritance for gene: SLC20A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4270 | PNPLA8 | Zornitza Stark Mode of inheritance for gene: PNPLA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4267 | NR2F1 | Zornitza Stark Mode of inheritance for gene: NR2F1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4264 | RAD50 | Zornitza Stark Mode of inheritance for gene: RAD50 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4260 | WASHC4 | Zornitza Stark Marked gene: WASHC4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4260 | WASHC4 | Zornitza Stark Gene: washc4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4260 | WASHC4 | Zornitza Stark Classified gene: WASHC4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4260 | WASHC4 | Zornitza Stark Gene: washc4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4259 | WASHC4 |
Zornitza Stark gene: WASHC4 was added gene: WASHC4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WASHC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WASHC4 were set to 31953988; 21498477 Phenotypes for gene: WASHC4 were set to Mental retardation, autosomal recessive 43, MIM #615817 Review for gene: WASHC4 was set to GREEN Added comment: Three unrelated families reported. Sources: Literature |
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| Mendeliome v0.4257 | DNAJC7 |
Seb Lunke gene: DNAJC7 was added gene: DNAJC7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAJC7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DNAJC7 were set to 31768050 Phenotypes for gene: DNAJC7 were set to amyotrophic lateral sclerosis Review for gene: DNAJC7 was set to AMBER Added comment: Two cohort studies in ALS patients identified 11 and 1 patient, respectively, with variants in DNAJC7. Seven of these are putative PTVs. However gene described as risk factor, unclear why. DOI: https://doi.org/10.1212/NXG.0000000000000503 Sources: Literature |
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| Mendeliome v0.4254 | HSPA9 | Zornitza Stark Mode of inheritance for gene: HSPA9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4253 | HSPA9 | Seb Lunke Mode of inheritance for gene: HSPA9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4251 | CFAP57 | Zornitza Stark Mode of inheritance for gene: CFAP57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4250 | SVIL |
Melanie Marty gene: SVIL was added gene: SVIL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SVIL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SVIL were set to 32779703 Phenotypes for gene: SVIL were set to myopathy Penetrance for gene: SVIL were set to unknown Review for gene: SVIL was set to GREEN Added comment: Four patients from two unrelated consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. Functional studies on muscle biopsies showed complete loss protein in muscle fibres by western blot. Sources: Literature |
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| Mendeliome v0.4250 | CFAP58 |
Crystle Lee gene: CFAP58 was added gene: CFAP58 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CFAP58 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP58 were set to 32791035 Phenotypes for gene: CFAP58 were set to Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035) Review for gene: CFAP58 was set to AMBER Added comment: 5 unrelated males reported with biallelic loss of function variants. Knockout mice were infertile (Abstract only) Sources: Expert Review |
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| Mendeliome v0.4250 | MYT1L | Zornitza Stark Tag SV/CNV tag was added to gene: MYT1L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4247 | ARID1A | Zornitza Stark Mode of inheritance for gene: ARID1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4244 | PDE10A | Zornitza Stark Mode of inheritance for gene: PDE10A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4239 | KIF1C | Zornitza Stark Mode of inheritance for gene: KIF1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4236 | GTPBP2 | Zornitza Stark Mode of inheritance for gene: GTPBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4233 | GNB1 | Zornitza Stark Mode of inheritance for gene: GNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4230 | MCM10 |
Zornitza Stark gene: MCM10 was added gene: MCM10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MCM10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM10 were set to 32865517 Phenotypes for gene: MCM10 were set to Susceptibility to CMV Review for gene: MCM10 was set to RED Added comment: Compound heterozygous variants in minichromosomal maintenance complex member 10 (MCM10) reported as a cause of NK-cell deficiency in a child with fatal susceptibility to CMV. Sources: Literature |
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| Mendeliome v0.4227 | FDXR | Zornitza Stark Mode of inheritance for gene: FDXR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4223 | EIF2S3 | Zornitza Stark Mode of inheritance for gene: EIF2S3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4218 | TRAPPC6B | Zornitza Stark Mode of inheritance for gene: TRAPPC6B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4215 | TRAPPC12 | Zornitza Stark Mode of inheritance for gene: TRAPPC12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4212 | TPRKB | Zornitza Stark Mode of inheritance for gene: TPRKB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4209 | TP53RK | Zornitza Stark Mode of inheritance for gene: TP53RK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4206 | TBC1D20 | Zornitza Stark Mode of inheritance for gene: TBC1D20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4205 | DHX34 |
Zornitza Stark gene: DHX34 was added gene: DHX34 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DHX34 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: DHX34 were set to 31256877 Phenotypes for gene: DHX34 were set to Intellectual disability; congenital anomalies Review for gene: DHX34 was set to RED Added comment: Three families reported. Two with bi-allelic variants and ID/multiple congenital anomalies but another molecular diagnosis present in both (variants in established genes). Single de novo missense in another individual with ID and dysmorphism. No supporting functional data. Overall RED rating for both MOI. Sources: Literature |
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| Mendeliome v0.4204 | DDX54 |
Zornitza Stark gene: DDX54 was added gene: DDX54 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DDX54 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: DDX54 were set to 31256877 Phenotypes for gene: DDX54 were set to Intellectual disability; congenital anomalies Review for gene: DDX54 was set to RED Added comment: Three individuals reported with different MOIs and different phenotypes. One with de novo variant and ID, another with bi-allelic variants and ID, and a third with bi-allelic variants and CAKUT. All variants are missense, no functional data. Overall, Red rating given inconsistent phenotypes and modes of inheritance, each one is essentially treated separately for now until further cases identified. Sources: Literature |
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| Mendeliome v0.4202 | DHX16 |
Zornitza Stark gene: DHX16 was added gene: DHX16 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DHX16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHX16 were set to 31256877 Phenotypes for gene: DHX16 were set to Neuromuscular disease and ocular or auditory anomalies with or without seizures, MIM# 618733 Review for gene: DHX16 was set to GREEN Added comment: Four unrelated individuals reported with de novo missense variants in this gene. Three of the individuals died in infancy, so phenotypic spectrum difficult to discern. Two had seizures. Individual with long-term survival had a progressive course, evidence of myopathy, loss of hearing and vision, and normal IQ. Sources: Literature |
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| Mendeliome v0.4199 | DHX37 | Zornitza Stark Mode of inheritance for gene: DHX37 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4196 | CFL2 | Zornitza Stark Mode of inheritance for gene: CFL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4191 | PAK3 | Zornitza Stark Mode of inheritance for gene: PAK3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4188 | CLTC | Zornitza Stark Mode of inheritance for gene: CLTC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4185 | RPL10 | Zornitza Stark Mode of inheritance for gene: RPL10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4182 | IFT122 | Zornitza Stark Mode of inheritance for gene: IFT122 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4174 | RARS2 | Zornitza Stark Mode of inheritance for gene: RARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4173 | RAD21 | Zornitza Stark Mode of inheritance for gene: RAD21 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4170 | RAB3GAP2 | Zornitza Stark Mode of inheritance for gene: RAB3GAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4167 | RAB3GAP1 | Zornitza Stark Mode of inheritance for gene: RAB3GAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4166 | RAB18 | Zornitza Stark Tag founder tag was added to gene: RAB18. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4164 | RAB18 | Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4161 | PTPN23 | Zornitza Stark Mode of inheritance for gene: PTPN23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4158 | PRUNE1 | Zornitza Stark Mode of inheritance for gene: PRUNE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4155 | POGZ | Zornitza Stark Mode of inheritance for gene: POGZ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4152 | POC1A | Zornitza Stark Mode of inheritance for gene: POC1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4149 | PLK4 | Zornitza Stark Mode of inheritance for gene: PLK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4146 | PIGH | Zornitza Stark Mode of inheritance for gene: PIGH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4144 | PCYT2 | Zornitza Stark Mode of inheritance for gene: PCYT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4143 | TRAPPC2L | Zornitza Stark Tag founder tag was added to gene: TRAPPC2L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4142 | TIMM8A | Zornitza Stark Mode of inheritance for gene: TIMM8A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4136 | DPP6 | Zornitza Stark Mode of inheritance for gene: DPP6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4134 | DPP6 | Zornitza Stark Tag SV/CNV tag was added to gene: DPP6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4134 | TRAPPC2L |
Arina Puzriakova changed review comment from: Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P. PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect. The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11. PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family. Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a. Sources: Literature; to: Total of three families, but two share a founder variant, and there are some disparities between the clinical presentations reported in the two publications. Rating Amber as additional cases required to delineate the genotype-phenotype relationship. PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect. The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11. PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family. Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a. Sources: Literature |
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| Mendeliome v0.4134 | TRAPPC2L |
Arina Puzriakova gene: TRAPPC2L was added gene: TRAPPC2L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRAPPC2L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC2L were set to 30120216; 32843486 Phenotypes for gene: TRAPPC2L were set to Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331 Review for gene: TRAPPC2L was set to AMBER Added comment: Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P. PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect. The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11. PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family. Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a. Sources: Literature |
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| Mendeliome v0.4134 | TOGARAM1 |
Arina Puzriakova gene: TOGARAM1 was added gene: TOGARAM1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TOGARAM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOGARAM1 were set to 32747439 Phenotypes for gene: TOGARAM1 were set to Cleft of the lip and palate; Microphthalmia; Cerebral dysgenesis; Hydrocephalus Added comment: PMID: 32747439 (2020) - Novel gene-disease association. In two sibling fetuses with a malformation disorder characterised by microcephaly, severe cleft lip and palate, microphthalmia, and brain anomalies, WES revealed compound heterozygous variants ([c.1102C>T, p.Arg368Trp] and [c.3619C>T, p.Arg1207*]) in the TOGARAM1 gene. Functional analysis of the missense variant in a C. elegans model showed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. In vitro analysis revealed faster microtubule polymerisation compared to wild-type, suggesting aberrant tubulin binding. Sources: Literature |
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| Mendeliome v0.4132 | PCGF2 | Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4129 | TRIT1 | Zornitza Stark Mode of inheritance for gene: TRIT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4126 | CREBBP | Zornitza Stark Mode of inheritance for gene: CREBBP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4125 | CRIPT |
Ain Roesley gene: CRIPT was added gene: CRIPT was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CRIPT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CRIPT were set to 24389050; 27250922 Phenotypes for gene: CRIPT were set to Short stature with microcephaly and distinctive facies (MIM#615789) Penetrance for gene: CRIPT were set to unknown Review for gene: CRIPT was set to AMBER Added comment: PMID: 24389050 - 2 unrelated probands homozygous for PTVs. However 1 was deceased and DNA was unavailable therefore parents were sequenced PMID: 27250922 - 1x proband - het for a missense which was maternally inherited. Because the father was negative for SNVs, they did CMA and found a small heterozygous deletion 1.6kb in size encompassing exon 1 of CRIPT. This deletion was paternally inherited *did not find new reports since Sources: Literature |
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| Mendeliome v0.4123 | DIAPH1 | Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4121 | UFC1 |
Paul De Fazio gene: UFC1 was added gene: UFC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UFC1 were set to 29868776; 30552426 Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth (MIM#618076) Review for gene: UFC1 was set to GREEN gene: UFC1 was marked as current diagnostic Added comment: PMID 29868776: 8 affected individuals from 4 families reported. 7 were described to be postnatally microcephalic (at or below 3rd percentile). One was -5.1SD and one was -3.6SD. SD values for the others weren't provided. The following head circumference measurements were provided for 6 of the affecteds: 51cm at 16yo; 50cm at 19yo; 42.5cm at 12mo, 45cm at 28mo, 45.2cm at 7yo; 45cm at 4yo. 3 of the families were consanguineous Saudi families with the same homozygous missense variant. In vitro functional expression studies showed that both mutations caused impaired thioester binding with UFM1. Patient cells also showed decreased UFC1 intermediate formation with UFM1. The decrease in function was consistent with a hypomorphic allele, and the authors suggested that complete loss of function would be embryonic lethal. PMID 30552426: 1 more individual with epileptic encephalopathy reported with a different homozygous missense variant in UFC1. The patient had microcephaly <3rd percentile. Sources: Literature |
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| Mendeliome v0.4119 | CENPE | Seb Lunke Mode of inheritance for gene: CENPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4115 | CDC6 | Seb Lunke Mode of inheritance for gene: CDC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4111 | CTNND1 | Zornitza Stark Mode of inheritance for gene: CTNND1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4107 | RIPOR2 | Zornitza Stark Mode of inheritance for gene: RIPOR2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4106 | RIPOR2 | Zornitza Stark Tag founder tag was added to gene: RIPOR2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4104 | TET2 | Zornitza Stark Mode of inheritance for gene: TET2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4099 | TRPM7 | Zornitza Stark Mode of inheritance for gene: TRPM7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4097 | CHCHD10 | Zornitza Stark Tag founder tag was added to gene: CHCHD10. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4095 | CHCHD10 | Zornitza Stark Mode of pathogenicity for gene: CHCHD10 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4094 | CHCHD10 | Zornitza Stark Mode of inheritance for gene: CHCHD10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4091 | NOTCH3 |
Eleanor Williams gene: NOTCH3 was added gene: NOTCH3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NOTCH3 were set to 31960911 Phenotypes for gene: NOTCH3 were set to CADASIL Review for gene: NOTCH3 was set to AMBER Added comment: PMID: 31960911 - Gravesteijn et al 2020 - describe a family with a unique cysteine-altering NOTCH3 variant in exon 9 in 5 individuals, which is predicted to cause natural exon 9 skipping. This mimics the therapeutic NOTCH3 cysteine correction approach and allows the effect of cysteine corrective exon skipping on NOTCH3 protein aggregation and disease severity in humans to be studied. In this family the CADASIL phenotype was mild. Note this gene is rated green on the Neurodegenerative disorders - adult onset panel in the Genomics England instance of PanelApp https://panelapp.genomicsengland.co.uk/panels/474/gene/NOTCH3/ Sources: Literature |
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| Mendeliome v0.4091 | ZFYVE19 |
Arina Puzriakova gene: ZFYVE19 was added gene: ZFYVE19 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZFYVE19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZFYVE19 were set to 32737136 Phenotypes for gene: ZFYVE19 were set to Cholestasis Review for gene: ZFYVE19 was set to GREEN Added comment: PMID: 32737136 (2020) - Nine Han Chinese children from seven families with biallelic, predicted complete LoF variants in ZFYVE19. All patients had high-GGT intrahepatic cholestasis, portal hypertension, and histopathological features of the ductal plate malformation/congenital hepatic fibrosis. ZFYVE19 depletion in cultured cells from one patient yielded centriolar and axonemal abnormalities, and immunostaining for two ciliary proteins DCDC2 and ACALT showed abnormal localisation in patient cholangiocytes, indicating this as a novel ciliopathy disorder. Sources: Literature |
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| Mendeliome v0.4091 | IARS | Zornitza Stark Tag new gene name tag was added to gene: IARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4089 | SRD5A3 | Zornitza Stark Mode of inheritance for gene: SRD5A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4086 | KIF14 | Zornitza Stark Mode of inheritance for gene: KIF14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4083 | KIF1BP | Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4082 | KIF1BP | Zornitza Stark Tag new gene name tag was added to gene: KIF1BP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4080 | TRIP11 | Zornitza Stark Mode of inheritance for gene: TRIP11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4077 | PRF1 | Zornitza Stark Mode of inheritance for gene: PRF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4074 | HLCS | Zornitza Stark Mode of inheritance for gene: HLCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4071 | CA5A | Zornitza Stark Mode of inheritance for gene: CA5A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4070 | CA5A | Zornitza Stark Tag SV/CNV tag was added to gene: CA5A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4068 | MOCS1 | Zornitza Stark Mode of inheritance for gene: MOCS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4065 | KDM1A | Zornitza Stark Mode of inheritance for gene: KDM1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4061 | COL11A1 | Zornitza Stark Mode of pathogenicity for gene: COL11A1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4060 | COL11A1 | Zornitza Stark Mode of inheritance for gene: COL11A1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4059 | GON7 | Zornitza Stark Tag founder tag was added to gene: GON7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4058 | YRDC |
Zornitza Stark gene: YRDC was added gene: YRDC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YRDC were set to 31481669 Phenotypes for gene: YRDC were set to Galloway-Mowat syndrome Review for gene: YRDC was set to GREEN Added comment: Three individuals from two unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data. Sources: Literature |
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| Mendeliome v0.4056 | GON7 |
Zornitza Stark gene: GON7 was added gene: GON7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GON7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GON7 were set to 31481669 Phenotypes for gene: GON7 were set to Galloway-Mowat syndrome Review for gene: GON7 was set to GREEN Added comment: 11 individuals from 5 families. Four of the families had the same homozygous variant, shared haplotype suggestive of founder effect. Clinical features included proteinuria, microcephaly, brain malformations and developmental delay. Supportive functional data. Sources: Literature |
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| Mendeliome v0.4053 | LAGE3 | Zornitza Stark Mode of inheritance for gene: LAGE3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4050 | LINGO1 | Zornitza Stark Mode of inheritance for gene: LINGO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4046 | OSGEP | Zornitza Stark Mode of inheritance for gene: OSGEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4045 | NUP107 | Zornitza Stark Tag founder tag was added to gene: NUP107. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4043 | NUP107 | Zornitza Stark Mode of inheritance for gene: NUP107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4040 | NSD2 | Zornitza Stark Mode of inheritance for gene: NSD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4037 | NCAPH | Zornitza Stark Mode of inheritance for gene: NCAPH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4034 | ATRIP |
Ain Roesley gene: ATRIP was added gene: ATRIP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATRIP were set to 23144622 Phenotypes for gene: ATRIP were set to Seckel Syndrome Penetrance for gene: ATRIP were set to unknown Review for gene: ATRIP was set to RED Added comment: PMID: 23144622; - 1x proband from a consanguineous family - progressive severe microcephaly (-9 to -10SD) - cHet for a nonsense and a splice Sources: Literature |
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| Mendeliome v0.4032 | AP4E1 | Zornitza Stark Mode of inheritance for gene: AP4E1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4029 | AP4B1 | Zornitza Stark Mode of inheritance for gene: AP4B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4026 | TSEN2 | Zornitza Stark Mode of inheritance for gene: TSEN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4023 | ZSWIM6 | Zornitza Stark Mode of inheritance for gene: ZSWIM6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4020 | ABCB11 | Zornitza Stark Mode of inheritance for gene: ABCB11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4017 | ABCB1 | Zornitza Stark Mode of inheritance for gene: ABCB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4015 | AASS | Zornitza Stark Tag disputed tag was added to gene: AASS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4013 | ABCA3 | Zornitza Stark Mode of inheritance for gene: ABCA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4010 | ABCA12 | Zornitza Stark Mode of inheritance for gene: ABCA12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4007 | ABCA1 | Zornitza Stark Mode of inheritance for gene: ABCA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4004 | AASS | Zornitza Stark Mode of inheritance for gene: AASS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4002 | AASS | Zornitza Stark changed review comment from: Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic. Given the broad range of clinical features and the presence of consanguinity in several families, there was not strong evidence for causality of symptoms. Hyperlysinemia is generally considered to be a benign metabolic variant rather than a disease entity.; to: Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic. Given the broad range of clinical features and the presence of consanguinity in several families, there was not strong evidence for causality of symptoms. It has been suggested that hyperlysinemia is a benign metabolic variant rather than a disease entity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4000 | AARS2 | Zornitza Stark Mode of inheritance for gene: AARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3997 | AARS | Zornitza Stark Mode of inheritance for gene: AARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3994 | AAGAB | Zornitza Stark Mode of inheritance for gene: AAGAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3991 | PAFAH1B1 | Zornitza Stark Tag SV/CNV tag was added to gene: PAFAH1B1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3989 | PAFAH1B1 | Zornitza Stark Mode of inheritance for gene: PAFAH1B1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3986 | LAMB1 | Zornitza Stark Mode of inheritance for gene: LAMB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3983 | TMEM5 | Zornitza Stark Mode of inheritance for gene: TMEM5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3980 | KIF5C | Zornitza Stark Mode of inheritance for gene: KIF5C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3977 | KIF2A | Zornitza Stark Mode of inheritance for gene: KIF2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3974 | ISPD | Zornitza Stark Mode of inheritance for gene: ISPD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3971 | DCX | Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3967 | MRPL44 | Zornitza Stark Mode of inheritance for gene: MRPL44 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3964 | KBTBD13 | Zornitza Stark Mode of inheritance for gene: KBTBD13 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3959 | LAMA2 | Zornitza Stark Mode of inheritance for gene: LAMA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3956 | GRIN2B | Zornitza Stark Mode of inheritance for gene: GRIN2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3953 | GRIN1 | Zornitza Stark Mode of inheritance for gene: GRIN1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3948 | SEC61A1 | Zornitza Stark Mode of inheritance for gene: SEC61A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3946 | ALG12 | Zornitza Stark Mode of inheritance for gene: ALG12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3943 | ALG11 | Zornitza Stark Mode of inheritance for gene: ALG11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3940 | NPRL2 | Zornitza Stark Mode of inheritance for gene: NPRL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3938 | PDE2A |
Zornitza Stark gene: PDE2A was added gene: PDE2A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDE2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE2A were set to 32467598; 32196122; 29392776 Phenotypes for gene: PDE2A were set to Paroxysmal dyskinesia Review for gene: PDE2A was set to GREEN Added comment: Four unrelated families reported with childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy. One of the reports characterises the disorder as 'Rett-like'. Sources: Literature |
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| Mendeliome v0.3935 | OTULIN | Zornitza Stark Mode of inheritance for gene: OTULIN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3932 | RRAGC | Zornitza Stark Mode of inheritance for gene: RRAGC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3926 | CRADD | Zornitza Stark Mode of inheritance for gene: CRADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3923 | TDGF1 | Zornitza Stark Mode of inheritance for gene: TDGF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3921 | GABRA6 |
Zornitza Stark gene: GABRA6 was added gene: GABRA6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GABRA6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRA6 were set to 21930603; 29215089; 19429026 Phenotypes for gene: GABRA6 were set to Benign familial inherited epilepsy; Childhood absence epilepsy Review for gene: GABRA6 was set to RED Added comment: One report in a cohort of patients with BFIE. Potential susceptibility allele in CAE. Sources: Literature |
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| Mendeliome v0.3918 | TMTC3 | Zornitza Stark Mode of inheritance for gene: TMTC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3915 | ARFGEF2 | Zornitza Stark Mode of inheritance for gene: ARFGEF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3912 | SLC6A3 | Zornitza Stark Mode of inheritance for gene: SLC6A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3909 | MAOA | Zornitza Stark Mode of inheritance for gene: MAOA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3908 | GPHN | Zornitza Stark Tag SV/CNV tag was added to gene: GPHN. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3906 | GPHN | Zornitza Stark Mode of inheritance for gene: GPHN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3903 | GLRB | Zornitza Stark Mode of inheritance for gene: GLRB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3902 | GLRA1 | Zornitza Stark Mode of inheritance for gene: GLRA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3899 | GLRA1 | Zornitza Stark Mode of inheritance for gene: GLRA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3896 | GABRG2 | Zornitza Stark Mode of inheritance for gene: GABRG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3893 | GABRB3 | Zornitza Stark Mode of inheritance for gene: GABRB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3890 | FOLR1 | Zornitza Stark Mode of inheritance for gene: FOLR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3887 | DBH | Zornitza Stark Mode of inheritance for gene: DBH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3884 | ARHGEF9 | Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3881 | STAT5B | Zornitza Stark Mode of pathogenicity for gene: STAT5B was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3880 | STAT5B | Zornitza Stark Mode of inheritance for gene: STAT5B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3877 | ALDH5A1 | Zornitza Stark Mode of inheritance for gene: ALDH5A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3874 | ABAT | Zornitza Stark Mode of inheritance for gene: ABAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3872 | LMBRD2 |
Zornitza Stark gene: LMBRD2 was added gene: LMBRD2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LMBRD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LMBRD2 were set to 32820033; https://doi.org/10.1101/797787 Phenotypes for gene: LMBRD2 were set to Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye Mode of pathogenicity for gene: LMBRD2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: LMBRD2 was set to GREEN Added comment: 13 individuals with dn missense SNVs overall, overlapping features for 10 with available phenotype / a recurring variant has been identified in 2 different studies. ► Malhotra et al (2020 - PMID: 32820033) report on 10 unrelated individuals with de novo missense LMBRD2 variants. Features included DD (9/10), ID (6/8 of relevant age), microcephaly (7/10), seizures (5/10 - >=3 different variants), structural brain abnormalities (e.g. thin CC in 6/9), highly variable ocular abnormalities (5/10) and dysmorphic features in some (7/10 - nonspecific). All had variable prior non-diagnostic genetic tests (CMA, gene panel, mendeliome, karyotype). WES/WGS revealed LMBRD2 missense variants, in all cases de novo. A single individual had additional variants with weaker evidence of pathogenicity. 5 unique missense SNVs and 2 recurrent ones (NM_001007527:c.367T>C - p.Trp123Arg / c.1448G>A - p.Arg483His) were identified. These occurred in different exons. Variants were not present in gnomAD and all had several in silico predictions in favor of a deleterious effect. There was phenotypic variability among individuals with the same variant (e.g. seizures in 1/3 and microchephaly in 2/3 of those harboring R483H). The gene has a pLI of 0 (although o/e ranges from 0.23 to 0.55), %HI of 15.13 and z-score of 2.27. The authors presume that haploinsufficiency may not apply, and consider a gain-of-function/dominant-negative effect more likely. As the authors comment LMBRD2 (LMBR1 domain containing 2) encodes a membrane bound protein with poorly described function. It is widely expressed across tissues with notable expression in human brain (also in Drosophila, or Xenopus laevis). It displays high interspecies conservation. It has been suggested (Paek et al - PMID: 28388415) that LMBRD2 is a potential regulator of β2 adrenoreceptor signalling through involvement in GPCR signalling. ► Kaplanis et al (2020 - https://doi.org/10.1101/797787) in a dataset of 31058 parent-offspring trios (WES) previously identified 3 individuals with developmental disorder, harboring c.1448G>A - p.Arg483His. These individuals (1 from the DDD study, and 2 GeneDx patients) appear in Decipher. [ https://decipher.sanger.ac.uk/ddd/research-variant/40e17c78cc9655a6721006fc1e0c98db/overview ]. The preprint by Kaplanis et al is cited by Malhotra et al, with Arg483His reported in 6 patients overall in both studies. Sources: Literature |
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| Mendeliome v0.3869 | KAT5 | Zornitza Stark Mode of pathogenicity for gene: KAT5 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3868 | KAT5 | Zornitza Stark Mode of inheritance for gene: KAT5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3864 | AFG3L2 | Zornitza Stark Mode of inheritance for gene: AFG3L2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3862 | MYOD1 |
Zornitza Stark gene: MYOD1 was added gene: MYOD1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MYOD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYOD1 were set to 26733463; 30403323; 31260566 Phenotypes for gene: MYOD1 were set to Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, MIM# 618975 Review for gene: MYOD1 was set to GREEN Added comment: Three unrelated families reported. Sources: Expert list |
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| Mendeliome v0.3860 | TMEM237 | Zornitza Stark Mode of inheritance for gene: TMEM237 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3857 | NOD2 | Zornitza Stark Mode of inheritance for gene: NOD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3854 | PAX3 | Zornitza Stark Mode of inheritance for gene: PAX3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3853 | KANSL1 | Zornitza Stark Tag SV/CNV tag was added to gene: KANSL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3851 | KANSL1 | Zornitza Stark Mode of inheritance for gene: KANSL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3848 | ESRRB | Zornitza Stark Mode of inheritance for gene: ESRRB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3846 | HNRNPA2B1 |
Zornitza Stark gene: HNRNPA2B1 was added gene: HNRNPA2B1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HNRNPA2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPA2B1 were set to 23455423; 30279180; 29358076; 26744327; 23635965 Phenotypes for gene: HNRNPA2B1 were set to Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 Review for gene: HNRNPA2B1 was set to AMBER Added comment: One family reported that segregates cognitive impairment as part of the phenotype, and extensive functional analysis of protein, including a drosophila model. Sources: Literature |
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| Mendeliome v0.3844 | PSMC3 |
Zornitza Stark gene: PSMC3 was added gene: PSMC3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMC3 were set to 32500975 Phenotypes for gene: PSMC3 were set to Deafness; cataract Review for gene: PSMC3 was set to AMBER Added comment: Three affected individuals from a single consanguineous family reported with homozygous intronic variant. Animal model. Sources: Literature |
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| Mendeliome v0.3841 | SOS2 | Zornitza Stark Mode of pathogenicity for gene: SOS2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3840 | SOS2 | Zornitza Stark Mode of inheritance for gene: SOS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3836 | RAI1 | Zornitza Stark Mode of inheritance for gene: RAI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3834 | TAF1C |
Zornitza Stark gene: TAF1C was added gene: TAF1C was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TAF1C were set to 32779182 Phenotypes for gene: TAF1C were set to Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology Review for gene: TAF1C was set to AMBER Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants. Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual). Following a normal CMA, exome in the first case revealed a homozygous missense SNV (NM_005679.3:c.1165C>T / p.Arg389Cys) supported by in silico predictions. mRNA and protein levels were substantially reduced in fibroblasts from this subject. Only the patient and parents were tested for the variant but not 3 unaffected sibs (fig1). The second individual was homozygous for another missense variant (p.Arg405Cys) also supported by in silico predictions. The girl was the single affected person within the family with an unaffected sib and parents heterozygous for the variant. Several other unaffected relatives in the extended pedigree were either carriers for this variant or homozygous for the wt allele. TAF1C encodes the TATA-box binding protein associated factor (TAF) RNA polymerase I subunit. RNA polymerase I (Pol I) transcribes genes to produce rRNA. For Pol I to initiate transcription, two transcription factors are required : UBF (upstream binding factor encoded by UBTF) and SL1 (selectivity factor 1). The latter is formed by TBP (TATA-binding protein) and 3 Pol I-specific TBP-associated factors (TAFs). A recurrent de novo missense variant in UBTF (encoding the other Pol I transcription factor) causes a disorder with highly similar features. The specific variant acts through a gain-of-function mechanism (and not by LoF which appears to apply for TAF1C based on expression data). The authors hypothesize that altered Pol I activity and resulting ribosomal stress could cause the microcephaly and leukodystrophy (both reported in 1 - the same - individual). Sources: Expert list |
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| Mendeliome v0.3831 | KALRN | Zornitza Stark Mode of inheritance for gene: KALRN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3827 | KRT6C | Zornitza Stark Mode of inheritance for gene: KRT6C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3824 | KRT6B | Zornitza Stark Mode of inheritance for gene: KRT6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3821 | KRT2 | Zornitza Stark Mode of inheritance for gene: KRT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3818 | KRT17 | Zornitza Stark Mode of inheritance for gene: KRT17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3815 | SERPINB7 | Zornitza Stark Mode of inheritance for gene: SERPINB7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3814 | SERPINB7 | Zornitza Stark Tag founder tag was added to gene: SERPINB7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3812 | SLURP1 | Zornitza Stark Mode of inheritance for gene: SLURP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3809 | ACTN4 | Zornitza Stark Mode of pathogenicity for gene: ACTN4 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3808 | ACTN4 | Zornitza Stark Mode of inheritance for gene: ACTN4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3807 | VKORC1 | Zornitza Stark Mode of inheritance for gene: VKORC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3805 | TPM4 |
Zornitza Stark gene: TPM4 was added gene: TPM4 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TPM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TPM4 were set to 28134622; 31249973; 21153663 Phenotypes for gene: TPM4 were set to Macrothrombocytopaenia Review for gene: TPM4 was set to GREEN Added comment: Three families reported in addition to genome-wide association studies in nearly 70,000 individuals which indicate that SNVs in TPM4 exert an effect on the count and volume of platelets. Sources: Expert list |
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| Mendeliome v0.3802 | THPO | Zornitza Stark Mode of inheritance for gene: THPO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3798 | TBXAS1 | Zornitza Stark Mode of inheritance for gene: TBXAS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3796 | SRC |
Zornitza Stark gene: SRC was added gene: SRC was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SRC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SRC were set to 31204551; 26936507 Phenotypes for gene: SRC were set to Thrombocytopaenia 6, MIM# 616937 Review for gene: SRC was set to GREEN Added comment: Two families, and convincing functional data including animal model. Sources: Expert list |
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| Mendeliome v0.3794 | SLFN14 |
Zornitza Stark gene: SLFN14 was added gene: SLFN14 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLFN14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLFN14 were set to 26280575; 26769223 Phenotypes for gene: SLFN14 were set to Bleeding disorder, platelet-type, 20, MIM# 616913 Review for gene: SLFN14 was set to GREEN Added comment: At least four unrelated families reported. Sources: Expert list |
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| Mendeliome v0.3792 | PTPRJ |
Zornitza Stark gene: PTPRJ was added gene: PTPRJ was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PTPRJ was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPRJ were set to 30591527 Phenotypes for gene: PTPRJ were set to Thrombocytopaenia Review for gene: PTPRJ was set to AMBER Added comment: Two siblings reported with nonsyndromic thrombocytopenia characterised by spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin. Supportive zebrafish model. Sources: Expert list |
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| Mendeliome v0.3790 | PTGS1 |
Zornitza Stark gene: PTGS1 was added gene: PTGS1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PTGS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTGS1 were set to 32299908; 11442478; 27629384; 8562397 Phenotypes for gene: PTGS1 were set to Platelet dysfunction; bleeding Review for gene: PTGS1 was set to AMBER Added comment: Single molecularly characterised family reported. However, note at least two previous older reports where deficiency was identified at protein rather than gene level. Sources: Expert list |
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| Mendeliome v0.3789 | PRKACG |
Zornitza Stark gene: PRKACG was added gene: PRKACG was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PRKACG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRKACG were set to 25061177; 30819905 Phenotypes for gene: PRKACG were set to Bleeding disorder, platelet-type, 19, MIM# 616176 Review for gene: PRKACG was set to RED Added comment: Single family reported only. A heterozygous VOUS reported in another individual in PMID 30819905 together with several other VOUS in same individual. Sources: Expert list |
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| Mendeliome v0.3787 | PLAU | Zornitza Stark Tag SV/CNV tag was added to gene: PLAU. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3787 | PLAU |
Zornitza Stark gene: PLAU was added gene: PLAU was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PLAU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLAU were set to 20007542 Phenotypes for gene: PLAU were set to Quebec platelet disorder, MIM# 601709 Review for gene: PLAU was set to GREEN Added comment: Note this is a tandem 78kb duplication of the gene, multiple families reported. Sources: Expert list |
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| Mendeliome v0.3785 | PLA2G4A |
Zornitza Stark gene: PLA2G4A was added gene: PLA2G4A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PLA2G4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLA2G4A were set to 18451993; 25102815; 23268370 Phenotypes for gene: PLA2G4A were set to Gastrointestinal ulceration, recurrent, with dysfunctional platelets, MIM# 618372 Review for gene: PLA2G4A was set to GREEN Added comment: At least three unrelated individuals reported. Sources: Expert list |
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| Mendeliome v0.3783 | MPIG6B |
Zornitza Stark gene: MPIG6B was added gene: MPIG6B was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MPIG6B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MPIG6B were set to 31276734; 29898956; 27743390 Phenotypes for gene: MPIG6B were set to Thrombocytopenia, anemia, and myelofibrosis, MIM# 617441 Review for gene: MPIG6B was set to GREEN Added comment: Six families reported. Sources: Expert list |
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| Mendeliome v0.3780 | MAT2A | Zornitza Stark Mode of inheritance for gene: MAT2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3776 | LOX | Zornitza Stark Mode of inheritance for gene: LOX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3773 | KDSR | Zornitza Stark Mode of inheritance for gene: KDSR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3770 | GGCX | Zornitza Stark Mode of inheritance for gene: GGCX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3767 | GPI | Zornitza Stark Mode of inheritance for gene: GPI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3764 | KANK2 | Zornitza Stark Mode of inheritance for gene: KANK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3763 | FAM83G |
Zornitza Stark gene: FAM83G was added gene: FAM83G was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FAM83G was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM83G were set to 29138053 Phenotypes for gene: FAM83G were set to Palmoplantar keratoderma, curly scalp hair and toenail dystrophy Review for gene: FAM83G was set to RED Added comment: PMID: 29138053; - 2 siblings born of consanguineous family presented with palmoplantar keratoderma and exuberant curly scalp hair - progressive development of yellowish thickened scaly skin affecting the palms and soles since 2 years of age, and toenail dystrophy in their teenage years > homozygous for a missense p.(Ala34Glu) Sources: Expert list |
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| Mendeliome v0.3759 | CAST | Zornitza Stark Mode of inheritance for gene: CAST was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3756 | CARD14 | Zornitza Stark Mode of inheritance for gene: CARD14 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3753 | TRPV3 | Zornitza Stark Mode of inheritance for gene: TRPV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3750 | EPHB2 | Zornitza Stark Mode of inheritance for gene: EPHB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3746 | ACTN1 | Zornitza Stark Mode of inheritance for gene: ACTN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3745 | DSG3 |
Zornitza Stark gene: DSG3 was added gene: DSG3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DSG3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DSG3 were set to 30528827 Phenotypes for gene: DSG3 were set to Mucosal blistering Review for gene: DSG3 was set to RED Added comment: One individual with recurrent blisters and erosions in the oral mucosa since birth homozygous for p(.R287*). Sources: Expert list |
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| Mendeliome v0.3741 | MADD | Zornitza Stark Mode of inheritance for gene: MADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3738 | UNC45A | Zornitza Stark Mode of inheritance for gene: UNC45A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3735 | HFE2 | Zornitza Stark Tag new gene name tag was added to gene: HFE2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3734 | HFE2 | Zornitza Stark Mode of inheritance for gene: HFE2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3732 | FAM50A |
Zornitza Stark gene: FAM50A was added gene: FAM50A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FAM50A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: FAM50A were set to 32703943 Phenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261) Review for gene: FAM50A was set to GREEN Added comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. The authors provide clinical details on 6 affected individuals from 5 families. Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40). Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish. Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins. Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.). Sources: Literature |
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| Mendeliome v0.3729 | ADK | Zornitza Stark Mode of inheritance for gene: ADK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3728 | SGK3 |
Zornitza Stark gene: SGK3 was added gene: SGK3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SGK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SGK3 were set to 31821448 Phenotypes for gene: SGK3 were set to Hypophosphatemic rickets Review for gene: SGK3 was set to RED Added comment: 5 individuals from one family where a splice site variant segregated with disease. Sources: Literature |
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| Mendeliome v0.3725 | SEC24D | Zornitza Stark Mode of inheritance for gene: SEC24D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3722 | P4HB | Zornitza Stark Mode of inheritance for gene: P4HB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3719 | MPDZ | Zornitza Stark Mode of inheritance for gene: MPDZ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3716 | B3GNT2 | Zornitza Stark Mode of inheritance for gene: B3GNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3713 | CNTN2 |
Zornitza Stark gene: CNTN2 was added gene: CNTN2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNTN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CNTN2 were set to 23518707 Phenotypes for gene: CNTN2 were set to Epilepsy Review for gene: CNTN2 was set to RED Added comment: Single family reported in 2013, supportive mouse model. Sources: Literature |
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| Mendeliome v0.3709 | DTNA | Zornitza Stark Mode of inheritance for gene: DTNA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3707 | HYLS1 | Zornitza Stark Tag founder tag was added to gene: HYLS1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3705 | HYLS1 | Zornitza Stark Mode of pathogenicity for gene: HYLS1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3704 | HYLS1 | Zornitza Stark Mode of inheritance for gene: HYLS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3700 | RAC1 | Zornitza Stark Mode of pathogenicity for gene: RAC1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3699 | RAC1 | Zornitza Stark Mode of inheritance for gene: RAC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3697 | FANCD2 | Zornitza Stark Mode of inheritance for gene: FANCD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3694 | BCOR | Zornitza Stark Mode of inheritance for gene: BCOR was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3692 | ARSE | Zornitza Stark Mode of inheritance for gene: ARSE was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3690 | ARSE | Zornitza Stark Tag new gene name tag was added to gene: ARSE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3688 | TPP1 | Zornitza Stark Mode of inheritance for gene: TPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3685 | PSAT1 | Zornitza Stark Mode of inheritance for gene: PSAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3682 | FBXO11 | Zornitza Stark Mode of inheritance for gene: FBXO11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3679 | FRMD7 | Zornitza Stark Mode of inheritance for gene: FRMD7 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3676 | AIFM1 | Zornitza Stark Mode of inheritance for gene: AIFM1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3675 | PIGQ |
Zornitza Stark edited their review of gene: PIGQ: Added comment: Homozygous or compound heterozygous mutations in PIGQ cause Epileptic encephalopathy, early infantile, 77 (MIM #618548). Johnstone et al (2020 - PMID: 32588908) describe the phenotype of 7 children (from 6 families) with biallelic PIGQ pathogenic variants. The authors also review the phenotype of 3 subjects previously reported in the literature (by Martin et al, Alazami et al, Starr et al - respective PMIDs: 24463883, 25558065, 31148362). Affected individuals displayed severe to profound global DD/ID and seizures with onset in the first year of life. There were variable other features incl. - among others - genitourinary, cardiac, skeletal, ophthalmological anomalies, gastrointestinal issues. Within the cohort there was significant morbidity/mortality. PIGQ encodes phosphatidylinositol glycan anchor biosynthesis class Q protein, playing a role (early) in the biosynthesis of the GPI-anchor. Several genes in the GPI biosynthesis pathway cause multi-system disease with DD/ID and seizures. Flow cytometry has been used in individuals with PIGQ-related disorder. Serum ALP was elevated in some (4) although - as the authors comment - elevations are more typical in disorders affecting later steps of GPI biosynthesis. More than 10 variants have been reported to date (missense / pLoF).; Changed phenotypes: Epileptic encephalopathy, early infantile, 77, MIM# 618548 |
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| Mendeliome v0.3673 | SEC61B |
Zornitza Stark gene: SEC61B was added gene: SEC61B was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SEC61B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEC61B were set to 28862642; 30652979; 28375157 Phenotypes for gene: SEC61B were set to Polycystic liver disease with or without renal cysts Review for gene: SEC61B was set to AMBER Added comment: Two unrelated individuals reported. Sources: Expert list |
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| Mendeliome v0.3669 | C3orf52 |
Zornitza Stark gene: C3orf52 was added gene: C3orf52 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C3orf52 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C3orf52 were set to 32336749 Phenotypes for gene: C3orf52 were set to Localized hypotrichosis Review for gene: C3orf52 was set to AMBER Added comment: 2 families with 4 individuals with localised hypotrichosis and homozygous variants in C3ORF52. C3ORF52 was found to be coexpressed with lipase H in the inner root sheath of the hair follicle and the two proteins were found to directly interact. The LAH-causing variants were associated with decreased C3ORF52 expression and resulted in markedly reduced lipase H–mediated 2-acyl-lysophosphatidic acid (LPA) biosynthesis. Same pathway as two other genes for localised hypotrichosis (LIPH and LPAR6) Sources: Literature |
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| Mendeliome v0.3668 | NDUFA8 |
Zornitza Stark gene: NDUFA8 was added gene: NDUFA8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NDUFA8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFA8 were set to 32385911 Phenotypes for gene: NDUFA8 were set to NDUFA8-related mitochondrial disease; Developmental delay; microcehaly; seizures Review for gene: NDUFA8 was set to RED Added comment: Single individual reported with homozygous variant, fibroblasts showed apparent biochemical defects in mitochondrial complex I. Sources: Literature |
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| Mendeliome v0.3666 | DLG5 |
Zornitza Stark gene: DLG5 was added gene: DLG5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DLG5 were set to 32631816 Phenotypes for gene: DLG5 were set to Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations Review for gene: DLG5 was set to GREEN Added comment: Four unrelated families reported, supportive Xenopus animal model data. Sources: Literature |
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| Mendeliome v0.3659 | RELN | Zornitza Stark Mode of inheritance for gene: RELN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3657 | CALCRL |
Hazel Phillimore gene: CALCRL was added gene: CALCRL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CALCRL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CALCRL were set to PMID: 30115739 Phenotypes for gene: CALCRL were set to ?Lymphatic malformation 8 (MIM# 618773); hydrops fetalis Review for gene: CALCRL was set to RED Added comment: Homozygous in-frame deletion (Val205del) in the CALCRL gene (Val205del) in a 22 week-old fetus with hydrops details due to lymphatic malformation. Consanguineous parents. Heterozygosity of the variant was also suggested to be associated with spontaneous miscarriage and subfertility. Consanguineous family with 8 total miscarriages from 3 carrier women, and 2 of these were confirmed to be due to hydrops fetalis. Note: possible association of a variant in ASAH1 gene that is associated with Farber lipogranulomatosis which can sometimes present with antenatal hydrops fetalis. (Homozygosity in one of the fetuses, fetus and heterozygosity in some of the family members). In vitro biochemical assays indicated that the variant causes misfolding of the protein and reduced association with its chaperone, RAMP2, and reduced translocation to the plasma membrane. (PMID: 30115739; Mackie, DI. et al., 2018). Sources: Literature |
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| Mendeliome v0.3657 | M1AP |
Ee Ming Wong gene: M1AP was added gene: M1AP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: M1AP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: M1AP were set to PMID: 32673564 Phenotypes for gene: M1AP were set to non-obstructive azoospermia (NOA); severe spermatogenic failure; male infertility Review for gene: M1AP was set to GREEN gene: M1AP was marked as current diagnostic Added comment: - One frameshift variant identified in 9 infertile men either in homozygous or compound heterozygous form - One missense variant segregated with infertility in five men from a consanguineous Turkish family Sources: Literature |
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| Mendeliome v0.3657 | AHR |
Chern Lim gene: AHR was added gene: AHR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AHR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AHR were set to 29726989; 31896775 Phenotypes for gene: AHR were set to ?Retinitis pigmentosa 85 MIM#618345; foveal hypoplasia and infantile nystagmus Review for gene: AHR was set to AMBER Added comment: - One reported homozygous splice variant in a consanguineous family & a mouse model (PMID: 29726989) - A homozygous nonsense variant in 1 consanguineous family with foveal hypoplasia and infantile nystagmus (PMID:31896775). Sources: Literature |
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| Mendeliome v0.3653 | CRY1 |
Ee Ming Wong gene: CRY1 was added gene: CRY1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CRY1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CRY1 were set to PMID: 28388406; PMID: 32538895 Phenotypes for gene: CRY1 were set to Attention deficit/hyperactivity disorder (ADHD); Delayed sleep phase disorder (DSPD), Penetrance for gene: CRY1 were set to Incomplete Review for gene: CRY1 was set to GREEN gene: CRY1 was marked as current diagnostic Added comment: - Splice variants identified in 7 families with ADHD and DSPD - Gain of function suggested for CRY1Δ11 (PMID: 28388406) - Loss of function suggested for CRY1Δ6 (HEK293T cells transfected with a Per1::Luc reporter plasmid showed reduced repressor activity compared to WT and CRY1Δ11) Sources: Literature |
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| Mendeliome v0.3648 | FBXL7 |
Hazel Phillimore changed review comment from: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous. Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae. Sources: Literature; to: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous. Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae. Sources: Literature |
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| Mendeliome v0.3647 | FBXL7 |
Hazel Phillimore gene: FBXL7 was added gene: FBXL7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FBXL7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FBXL7 were set to PMID: 31633297 Phenotypes for gene: FBXL7 were set to Hennekam lymphangiectasia-lymphedema syndrome; lymphedema; protein‐losing enteropathy; dental anomalies; camptodactyly; microtia; small auditory canals; ductive hearing loss; middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae. Review for gene: FBXL7 was set to AMBER Added comment: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous. Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae. Sources: Literature |
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| Mendeliome v0.3647 | HPDL |
Crystle Lee gene: HPDL was added gene: HPDL was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HPDL were set to 32707086 Phenotypes for gene: HPDL were set to Neurological disorder Review for gene: HPDL was set to GREEN Added comment: Biallelic variants reported in 13 families with a neurodegenerative disease ranging from neonatal encephalopathy to adolescent-onset spastic paraplegia Sources: Expert Review |
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| Mendeliome v0.3646 | PJA1 |
Zornitza Stark gene: PJA1 was added gene: PJA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PJA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PJA1 were set to 32530565 Phenotypes for gene: PJA1 were set to Intellectual disability; trigonocephaly Review for gene: PJA1 was set to AMBER Added comment: Recurrent variant, p.Arg376Cys, reported in 7 Japanese individuals, supportive mouse model. Individuals shared a common haplotype, suggestive of founder effect Sources: Literature |
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| Mendeliome v0.3645 | MYLPF |
Crystle Lee gene: MYLPF was added gene: MYLPF was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: MYLPF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MYLPF were set to 32707087 Phenotypes for gene: MYLPF were set to Distal arthrogryoposis Review for gene: MYLPF was set to GREEN Added comment: 2 different homozygous variants reported in 6 consanguineous families with DA and an additional 2 different dominantly inherited variants in 2 families, with supporting animal model. Sources: Expert Review |
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| Mendeliome v0.3645 | NCKAP1L |
Michelle Torres gene: NCKAP1L was added gene: NCKAP1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NCKAP1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NCKAP1L were set to 32647003 Phenotypes for gene: NCKAP1L were set to Immunodeficiency Review for gene: NCKAP1L was set to GREEN Added comment: 5 patients from 4 families with recurrent bacterial and viral skin infections, severe respiratory tract infections leading to pneumonia and bronchiectasis. Functional of the 4 missense reported were performed. Sources: Literature |
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| Mendeliome v0.3645 | MCF2 |
Zornitza Stark gene: MCF2 was added gene: MCF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MCF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: MCF2 were set to 31846234 Phenotypes for gene: MCF2 were set to Perisylvian polymicrogyria Review for gene: MCF2 was set to RED Added comment: Single individual reported, inherited missense variant from unaffected mother, some support from mouse model. Sources: Literature |
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| Mendeliome v0.3644 | SCAF4 |
Crystle Lee gene: SCAF4 was added gene: SCAF4 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SCAF4 were set to 32730804 Phenotypes for gene: SCAF4 were set to Mild intellectual disability; seizures; behavioral abnormalities Review for gene: SCAF4 was set to GREEN Added comment: > 5 variants reported in individuals with variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. Sources: Expert Review |
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| Mendeliome v0.3643 | NARS |
Zornitza Stark gene: NARS was added gene: NARS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NARS were set to 32738225 Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy Review for gene: NARS was set to GREEN Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). Sources: Literature |
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| Mendeliome v0.3640 | ZNF407 | Zornitza Stark Mode of inheritance for gene: ZNF407 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3636 | DDX58 | Zornitza Stark Mode of inheritance for gene: DDX58 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3633 | SYNE2 | Zornitza Stark Tag disputed tag was added to gene: SYNE2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3631 | MAPK1 |
Zornitza Stark gene: MAPK1 was added gene: MAPK1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAPK1 were set to 32721402 Phenotypes for gene: MAPK1 were set to Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin Review for gene: MAPK1 was set to GREEN Added comment: Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants. The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once. MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway. MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic). The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome). Sources: Literature |
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| Mendeliome v0.3628 | ASPM | Zornitza Stark Mode of inheritance for gene: ASPM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3626 | AMBRA1 |
Bryony Thompson gene: AMBRA1 was added gene: AMBRA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AMBRA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AMBRA1 were set to 17589504; 32333458 Phenotypes for gene: AMBRA1 were set to Neural tube defects Review for gene: AMBRA1 was set to GREEN Added comment: 5 rare missense variants were identified in 6 cases from a neural tube defect cohort, and 4 (p.Thr80Met, p.Leu274Phe, p.Ser743Phe, and p.Met884Val) of them were functionally validated to affect autophagy regulation in vitro or zebrafish embryo development in vivo. There is also null mouse model with neural tube defects. Sources: Literature |
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| Mendeliome v0.3624 | ERLEC1 |
Bryony Thompson gene: ERLEC1 was added gene: ERLEC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ERLEC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ERLEC1 were set to 32442352 Phenotypes for gene: ERLEC1 were set to Class III malocclusion Review for gene: ERLEC1 was set to GREEN Added comment: A heterozygous missense variant was found to co-segregate with dentofacial deformity in a multi-generational Chinese pedigree (2 unaffected carriers & 11 affected carriers), and 3 additional missense variants were identified in 3 unrelated cases from a sporadic malocclusion cohort. Additional functional assays were conducted to demonstrate that the proper level of ERLEC1 expression is crucial for proper osteogenic differentiation. All identified missense variants were assessed using luciferase reporter assays, and altered activity. Sources: Literature |
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| Mendeliome v0.3620 | WDR1 | Zornitza Stark Mode of inheritance for gene: WDR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3618 | KREMEN1 |
Bryony Thompson gene: KREMEN1 was added gene: KREMEN1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: KREMEN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KREMEN1 were set to 27049303; 27550540 Phenotypes for gene: KREMEN1 were set to Ectodermal dysplasia 13, hair/tooth type MIM#617392 Review for gene: KREMEN1 was set to AMBER Added comment: 4 consanguineous Palestinian families segregating the same homozygous missense (Phe209Ser) with disease phenotype which includes hair abnormalities. Possible founder variant. There are also animal model functional assays that suggest the gene is involved in hair development. Sources: Expert list |
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| Mendeliome v0.3612 | TUBB2A | Zornitza Stark Mode of inheritance for gene: TUBB2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3609 | PMP22 | Zornitza Stark Mode of inheritance for gene: PMP22 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3608 | PMP22 | Zornitza Stark Tag SV/CNV tag was added to gene: PMP22. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3607 | OTX2 | Zornitza Stark Mode of inheritance for gene: OTX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3604 | CDAN1 | Zornitza Stark Mode of inheritance for gene: CDAN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3601 | NGLY1 | Zornitza Stark Mode of inheritance for gene: NGLY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3599 | IMPG2 | Zornitza Stark Mode of inheritance for gene: IMPG2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3596 | IMPG2 | Zornitza Stark Mode of inheritance for gene: IMPG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3594 | EEF1A2 | Zornitza Stark Mode of inheritance for gene: EEF1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3591 | EEF1A2 | Zornitza Stark Mode of pathogenicity for gene: EEF1A2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3590 | ANO1 |
Arina Puzriakova changed review comment from: PMID: 32487539 (2020) - Two affected sibs presenting in early infancy with impaired intestinal peristalsis, intestinal pneumatosis and dysmorphic features. Delayed motor and language development was reported in one sibling, however, the other sibling died at 5 months from cardiac arrest and therefore a psychomotor assessment was performed. Exome sequencing identified a homozygous truncating variant (c.897+3_897+6delAAGT, p.L300Vfs*58) in ANO1 which segregated with disease in the family. Functional data revealed that the variant led to lack of expression of functional TMEM16A in patient cells, which in turn abolished calcium-activated Cl- currents. Also supportive mouse model. Sources: Literature; to: PMID: 32487539 (2020) - Two affected sibs presenting in early infancy with impaired intestinal peristalsis, intestinal pneumatosis and dysmorphic features. Delayed motor and language development was reported in one sibling, however, the other sibling died at 5 months from cardiac arrest and therefore a psychomotor assessment was not performed. Exome sequencing identified a homozygous truncating variant (c.897+3_897+6delAAGT, p.L300Vfs*58) in ANO1 which segregated with disease in the family. Functional data revealed that the variant led to lack of expression of functional TMEM16A in patient cells, which in turn abolished calcium-activated Cl- currents. Also supportive mouse model. Sources: Literature |
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| Mendeliome v0.3590 | ANO1 |
Arina Puzriakova gene: ANO1 was added gene: ANO1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ANO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ANO1 were set to 32487539 Added comment: PMID: 32487539 (2020) - Two affected sibs presenting in early infancy with impaired intestinal peristalsis, intestinal pneumatosis and dysmorphic features. Delayed motor and language development was reported in one sibling, however, the other sibling died at 5 months from cardiac arrest and therefore a psychomotor assessment was performed. Exome sequencing identified a homozygous truncating variant (c.897+3_897+6delAAGT, p.L300Vfs*58) in ANO1 which segregated with disease in the family. Functional data revealed that the variant led to lack of expression of functional TMEM16A in patient cells, which in turn abolished calcium-activated Cl- currents. Also supportive mouse model. Sources: Literature |
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| Mendeliome v0.3590 | GNPNAT1 |
Arina Puzriakova gene: GNPNAT1 was added gene: GNPNAT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GNPNAT1 were set to 32591345 Phenotypes for gene: GNPNAT1 were set to Rhizomelic skeletal dysplasia Review for gene: GNPNAT1 was set to RED Added comment: Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype. Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation. Sources: Literature |
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| Mendeliome v0.3588 | PKD1L1 | Zornitza Stark Mode of inheritance for gene: PKD1L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3586 | IVNS1ABP |
Bryony Thompson gene: IVNS1ABP was added gene: IVNS1ABP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IVNS1ABP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IVNS1ABP were set to 32499645 Phenotypes for gene: IVNS1ABP were set to Primary immunodeficiency Review for gene: IVNS1ABP was set to GREEN Added comment: 3 unrelated families with putative loss of function variants. Case features and immunophenotyping of patient cells is suggestive of a combined immune deficiency, based on the ESID definitions of PID subtypes. Sources: Literature |
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| Mendeliome v0.3584 | PTPN2 |
Bryony Thompson gene: PTPN2 was added gene: PTPN2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTPN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PTPN2 were set to 32499645; 27658548 Phenotypes for gene: PTPN2 were set to Lupus; arthritis; common variable immunodeficiency Review for gene: PTPN2 was set to AMBER Added comment: A single family with a proband diagnosed with CVID and arthiritis (among other features) with an intronic expression quantitative trait loci (eQTL) rs2847297-G in trans with a stopgain variant. The stopgain variant was also identified in the proband's mother, who was diagnosed with lupus. A Ptpn2 deficient mouse model also demonstrates an autoimmune phenotype. Sources: Literature |
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| Mendeliome v0.3582 | SOCS1 |
Bryony Thompson gene: SOCS1 was added gene: SOCS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SOCS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SOCS1 were set to 32499645; 10490099; 10490100 Phenotypes for gene: SOCS1 were set to Common variable immunodeficiency Review for gene: SOCS1 was set to GREEN Added comment: 2 unrelated families with truncating variants with supportive immunophenotyping of patient cells, and supporting null mouse models. Sources: Literature |
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| Mendeliome v0.3576 | OXCT1 | Zornitza Stark Mode of inheritance for gene: OXCT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3573 | KCNJ1 | Zornitza Stark Mode of inheritance for gene: KCNJ1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3570 | ZFYVE27 | Zornitza Stark Mode of inheritance for gene: ZFYVE27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3566 | MYOZ2 | Zornitza Stark Mode of inheritance for gene: MYOZ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3562 | PDLIM3 | Zornitza Stark Tag SV/CNV tag was added to gene: PDLIM3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3561 | OBSCN |
Paul De Fazio gene: OBSCN was added gene: OBSCN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: OBSCN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: OBSCN were set to 30681346; 26573135; 17716621; 25173926; 28630914 Phenotypes for gene: OBSCN were set to Hypertrophic cardiomyopathy Review for gene: OBSCN was set to RED gene: OBSCN was marked as current diagnostic Added comment: Limited evidence by ClinGen working group. Via ClinGen: 8 probands in 3 publications but only 3 probands from 1 publication were though to have pathogenic variants (others were excluded based on population frequency and expert review). No additional case reports were found. A mouse model lends some support to the association of this gene with heart disease although not HCM specifically. Sources: Literature |
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| Mendeliome v0.3561 | PDLIM3 |
Ain Roesley gene: PDLIM3 was added gene: PDLIM3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDLIM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PDLIM3 were set to 30681346; 26455666; 20801532 Phenotypes for gene: PDLIM3 were set to Hypertrophic cardiomyopathy Penetrance for gene: PDLIM3 were set to unknown Added comment: PMID: 30681346; LIMITED by ClinGen working group PMID: 26455666; 1x proband with multi-exon deletion PMID: 20801532; 1x proband het for a missense Sources: Literature |
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| Mendeliome v0.3561 | TRIM63 |
Ain Roesley gene: TRIM63 was added gene: TRIM63 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRIM63 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRIM63 were set to 30681346; 32451364 Phenotypes for gene: TRIM63 were set to Hypertrophic cardiomyopathy Penetrance for gene: TRIM63 were set to unknown Review for gene: TRIM63 was set to GREEN Added comment: PMID: 30681346; LIMITED by Clingen working group (last evaluated 2018) PMID: 32451364 - 16 index cases with rare homozygous or compound heterozygous variants (15 HCM and one restrictive cardiomyopathy). None of these variants have homozygote counts in gnomAD. - segregated in 3 families - 1 index had another pathogenic truncating variant in MYBPC3 - 5 missense and 3 PTCs - Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy Sources: Literature |
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| Mendeliome v0.3561 | KLF10 |
Paul De Fazio gene: KLF10 was added gene: KLF10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLF10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KLF10 were set to 22234868 Phenotypes for gene: KLF10 were set to HCM gene: KLF10 was marked as current diagnostic Added comment: Curated by ClinGen and rated as limited evidence. Misssense mutations reported in six unrelated individuals patients (two males/four females), with family history of HCM only reported for one individual (PMID: 22234868). No further reports in the literature. Sources: Literature |
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| Mendeliome v0.3560 | KRT71 |
Bryony Thompson gene: KRT71 was added gene: KRT71 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KRT71 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KRT71 were set to 14632181; 22592156; 19713490 Phenotypes for gene: KRT71 were set to ?Hypotrichosis 13, 615896 Review for gene: KRT71 was set to AMBER Added comment: A single family with 3 affected members of a 3-generation Japanese family segregating a missense variant (F141C) with autosomal dominant woolly hair/hypotrichosis, with supporting functional assays and animal models. Sources: Literature |
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| Mendeliome v0.3559 | ACADL | Zornitza Stark Tag disputed tag was added to gene: ACADL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3557 | ACADL | Zornitza Stark Mode of inheritance for gene: ACADL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3553 | TWNK | Zornitza Stark Mode of pathogenicity for gene: TWNK was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3552 | TWNK | Zornitza Stark Mode of inheritance for gene: TWNK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3551 | UBE2T | Zornitza Stark Tag SV/CNV tag was added to gene: UBE2T. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3548 | P2RX2 | Zornitza Stark Mode of inheritance for gene: P2RX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3545 | KCNQ4 | Zornitza Stark Mode of inheritance for gene: KCNQ4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3542 | FLCN | Zornitza Stark Mode of inheritance for gene: FLCN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3539 | LARS |
Zornitza Stark Added comment: Comment when marking as ready: Lenz et al (2020 - PMID: 32699352) review the phenotype of 25 affected individuals from 15 families. Seizures occurred in 19/24 and were commonly associated with infections. Encephalopathic episodes (in 13 patients) accompanied by seizures up to status epilepticus occurred independently of hepatic decompensation. In addition 22/24 presented with neurodevelopmental delay. The authors comment that cognitive impairment was present in 13/17 individuals (mild-severe) whereas most presented with learning disabilities. These patients will most likely investigated for their liver disease (although presentation was highly variable and/or very mild in few). The gene encodes a cytoplasmic amino-acyl tRNA synthetase (ARS) with neurologic manifestations observed in almost all patients (and seizures / DD and ID common to other disorders due to mutations in other genes encoding for ARSs). Please note that the HGNC approved symbol for this gene is LARS1. |
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| Mendeliome v0.3539 | LARS | Zornitza Stark Tag new gene name tag was added to gene: LARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3537 | KERA | Zornitza Stark Mode of inheritance for gene: KERA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3534 | CTRC | Zornitza Stark Mode of inheritance for gene: CTRC was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3530 | CPA1 | Zornitza Stark Mode of inheritance for gene: CPA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3527 | CLDN2 | Zornitza Stark Mode of inheritance for gene: CLDN2 was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3524 | BMP10 |
Zornitza Stark gene: BMP10 was added gene: BMP10 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: BMP10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BMP10 were set to 30578383 Phenotypes for gene: BMP10 were set to Pulmonary arterial hypertension Review for gene: BMP10 was set to AMBER Added comment: A truncating mutation and a predicted loss-of-function missense variant were identified in BMP10 in two severely affected sporadic PAH female patients. Sources: Expert list |
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| Mendeliome v0.3522 | SMAD1 |
Zornitza Stark gene: SMAD1 was added gene: SMAD1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SMAD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMAD1 were set to 21898662; 23478097 Phenotypes for gene: SMAD1 were set to Pulmonary arterial hypertension Review for gene: SMAD1 was set to AMBER Added comment: One missense variant identified in a PAH case. Mouse model is consistent with pulmonary hypertension. Sources: Expert list |
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| Mendeliome v0.3521 | BRAP |
Zornitza Stark gene: BRAP was added gene: BRAP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: BRAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BRAP were set to 30703135 Phenotypes for gene: BRAP were set to Pulmonary arterial hypertension Review for gene: BRAP was set to RED Added comment: A single BRAP missense variant in a Japanese family with PAH, with in vitro functional assays suggesting a gain-of-function. Sources: Expert list |
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| Mendeliome v0.3520 | KLF2 |
Zornitza Stark gene: KLF2 was added gene: KLF2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: KLF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLF2 were set to 28188237 Phenotypes for gene: KLF2 were set to Pulmonary arterial hypertension Review for gene: KLF2 was set to RED Added comment: Single family reported. Sources: Expert list |
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| Mendeliome v0.3518 | ATP13A3 |
Zornitza Stark gene: ATP13A3 was added gene: ATP13A3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ATP13A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP13A3 were set to 31798832; 30679663; 29650961 Phenotypes for gene: ATP13A3 were set to Pulmonary arterial hypertension Review for gene: ATP13A3 was set to GREEN Added comment: Three heterozygous frameshift variants, three stop gained, two splice region variants in ATP13A3, which are predicted to lead to loss of ATPase catalytic activity identified in idiopathic/familial PAH cases. Also one case with putative recessive inheritance reported. ATP13A3 mRNA expression is confirmed in primary PASMCs and endothelial cells where its loss hindered proliferation and enhanced apoptosis of endothelial cells, which is known as the initiation event of PAH. Sources: Expert list |
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| Mendeliome v0.3515 | SMARCA2 | Zornitza Stark Mode of pathogenicity for gene: SMARCA2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3514 | SMARCA2 | Zornitza Stark Mode of inheritance for gene: SMARCA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3511 | MORC2 | Zornitza Stark Mode of inheritance for gene: MORC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3508 | DBT | Zornitza Stark Mode of inheritance for gene: DBT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3507 | PLCB3 |
Zornitza Stark gene: PLCB3 was added gene: PLCB3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PLCB3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLCB3 were set to 29122926 Phenotypes for gene: PLCB3 were set to Spondylometaphyseal dysplasia with corneal dystrophy, MIM# 618961 Review for gene: PLCB3 was set to RED Added comment: Single consanguineous family reported. Sources: Expert list |
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| Mendeliome v0.3504 | ACOX1 | Zornitza Stark Mode of inheritance for gene: ACOX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3500 | MPL | Zornitza Stark Mode of inheritance for gene: MPL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3497 | SH2B3 | Zornitza Stark Mode of inheritance for gene: SH2B3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3494 | HPD | Zornitza Stark Mode of inheritance for gene: HPD was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3491 | FANCM | Zornitza Stark Mode of inheritance for gene: FANCM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3487 | HDAC8 | Zornitza Stark Mode of inheritance for gene: HDAC8 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3486 | RBM8A | Zornitza Stark Tag SV/CNV tag was added to gene: RBM8A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3485 | RBM8A | Zornitza Stark Mode of inheritance for gene: RBM8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3482 | RPL15 | Zornitza Stark Mode of inheritance for gene: RPL15 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3479 | RPS28 | Zornitza Stark Mode of inheritance for gene: RPS28 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3475 | RPS29 | Zornitza Stark Mode of inheritance for gene: RPS29 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3473 | UMOD | Zornitza Stark Mode of inheritance for gene: UMOD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3470 | REN | Zornitza Stark Mode of inheritance for gene: REN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3465 | UVSSA | Zornitza Stark Mode of inheritance for gene: UVSSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3462 | SEC23A | Zornitza Stark Mode of inheritance for gene: SEC23A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3456 | VPS33A | Zornitza Stark Mode of inheritance for gene: VPS33A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3452 | COG2 | Zornitza Stark Mode of inheritance for gene: COG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3450 | DACT1 |
Natalie Tan gene: DACT1 was added gene: DACT1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: DACT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DACT1 were set to PMID: 28054444; 22610794; 19701191 Phenotypes for gene: DACT1 were set to ?Townes-Brocks syndrome 2 (OMIM #617466) Review for gene: DACT1 was set to RED Added comment: Webb et al. (2017) reported 6 affected members of a 3-generation family with ?Townes-Brocks syndrome-2, identified heterozygosity for a nonsense mutation in the DACT1 gene that segregated with disease. Clinical features include imperforate anus, rectovaginal fistula, crossed fused renal ectopia, vesicoureteral reflux, unilateral microtia, overfolded helices and cupped ears. One family member (proband's mother) with scoliosis and spina bifida occulta. Neural tube defects reported in a study of human fetuses (PMID: 22610794) and a mouse model (PMID: 19701191). Listed in Decipher v10.0 for an individual with abnormalities of (i) head or neck (ii) nervous system (iii) skeletal system. Unlike the gene SALL1 that causes Townes-Brocks syndrome 1, there is no information specifically relating to DACT1 with radial dysplasia, as these were not observed in the family with ?Townes-Brocks syndrome 2 (PMID: 28054444). Sources: NHS GMS |
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| Mendeliome v0.3448 | G6PC3 | Zornitza Stark Mode of inheritance for gene: G6PC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3445 | POGLUT1 | Zornitza Stark Mode of inheritance for gene: POGLUT1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3442 | ARSG | Zornitza Stark Tag founder tag was added to gene: ARSG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3440 | FAM92A |
Zornitza Stark gene: FAM92A was added gene: FAM92A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM92A were set to 30395363 Phenotypes for gene: FAM92A were set to Polydactyly, postaxial, type A9, MIM# 618219 Review for gene: FAM92A was set to AMBER Added comment: Single family and a mouse model reported. Sources: Expert list |
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| Mendeliome v0.3438 | KIAA0825 |
Zornitza Stark gene: KIAA0825 was added gene: KIAA0825 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIAA0825 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0825 were set to 32147526; 30982135 Phenotypes for gene: KIAA0825 were set to Polydactyly, postaxial, type A10, MIM# 618498 Review for gene: KIAA0825 was set to GREEN Added comment: Three unrelated families reported. Sources: Literature |
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| Mendeliome v0.3435 | ZNF141 | Zornitza Stark Mode of inheritance for gene: ZNF141 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3430 | NR0B1 | Zornitza Stark Tag SV/CNV tag was added to gene: NR0B1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3428 | NR0B1 | Zornitza Stark Mode of inheritance for gene: NR0B1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3425 | NSDHL | Zornitza Stark Mode of inheritance for gene: NSDHL was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3424 | TFR2 | Zornitza Stark Mode of inheritance for gene: TFR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3420 | TFR2 | Zornitza Stark Mode of inheritance for gene: TFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3417 | ABCD3 | Zornitza Stark Mode of inheritance for gene: ABCD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3410 | NSMF | Zornitza Stark Mode of inheritance for gene: NSMF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3408 | SPRY4 | Zornitza Stark Tag disputed tag was added to gene: SPRY4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3406 | SPRY4 | Zornitza Stark Mode of inheritance for gene: SPRY4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3402 | KISS1 | Zornitza Stark Mode of inheritance for gene: KISS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3398 | INSL3 | Zornitza Stark Mode of inheritance for gene: INSL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3394 | IL17RD | Zornitza Stark Mode of inheritance for gene: IL17RD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3392 | HS6ST1 | Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3389 | HS6ST1 | Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3385 | GNRH1 | Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3381 | CUX2 | Zornitza Stark Mode of inheritance for gene: CUX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3378 | DPM1 | Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3376 | GIPC1 |
Zornitza Stark gene: GIPC1 was added gene: GIPC1 was added to Mendeliome. Sources: Literature 5'UTR, STR tags were added to gene: GIPC1. Mode of inheritance for gene: GIPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GIPC1 were set to 32413282 Phenotypes for gene: GIPC1 were set to Oculopharyngodistal myopathy-2 (OPDM2), MIM#618940 Review for gene: GIPC1 was set to AMBER Added comment: 19 families reported with heterozygous trinucleotide repeat expansion in the 5-prime untranslated region and onset of distal muscle weakness, mainly of the lower limbs, and/or ophthalmoplegia in the second or third decades of life. Note this is unlikely to be tractable currently by most NGS assays. Sources: Literature |
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| Mendeliome v0.3373 | SMC3 | Zornitza Stark Mode of inheritance for gene: SMC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3370 | DEAF1 | Zornitza Stark Mode of pathogenicity for gene: DEAF1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3369 | DEAF1 | Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3364 | ABCC9 | Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3361 | TSPYL1 | Zornitza Stark Mode of inheritance for gene: TSPYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3357 | PIGM | Zornitza Stark Mode of inheritance for gene: PIGM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3355 | PIGM | Zornitza Stark Tag founder tag was added to gene: PIGM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3353 | LEP | Zornitza Stark Mode of inheritance for gene: LEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3350 | LEPR | Zornitza Stark Mode of inheritance for gene: LEPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3347 | FEZF1 | Zornitza Stark Mode of inheritance for gene: FEZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3343 | ESR2 | Zornitza Stark Mode of inheritance for gene: ESR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3340 | DMRT1 | Zornitza Stark Mode of inheritance for gene: DMRT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3336 | CBX2 | Zornitza Stark Mode of inheritance for gene: CBX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3331 | MCM5 |
Crystle Lee gene: MCM5 was added gene: MCM5 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM5 were set to 28198391 Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8 (MIM#617564) Review for gene: MCM5 was set to RED Added comment: Compound heterozgyous variants reported in one patient. Insufficient evidence supporting gene disease association Sources: Expert Review |
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| Mendeliome v0.3329 | CNPY3 | Zornitza Stark Mode of inheritance for gene: CNPY3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3327 | KIF21B |
Zornitza Stark gene: KIF21B was added gene: KIF21B was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF21B were set to 32415109 Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly Mode of pathogenicity for gene: KIF21B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: KIF21B was set to GREEN Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors). Sources: Expert Review |
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| Mendeliome v0.3325 | TBC1D2B |
Zornitza Stark gene: TBC1D2B was added gene: TBC1D2B was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D2B were set to 32623794 Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality Review for gene: TBC1D2B was set to GREEN Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24. Sources: Expert Review |
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| Mendeliome v0.3323 | EXOC2 |
Zornitza Stark gene: EXOC2 was added gene: EXOC2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC2 were set to 32639540 Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology Review for gene: EXOC2 was set to AMBER Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants). Sources: Expert Review |
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| Mendeliome v0.3321 | CCDC174 |
Zornitza Stark gene: CCDC174 was added gene: CCDC174 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC174 were set to 26358778 Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816 Review for gene: CCDC174 was set to AMBER Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports. Sources: Expert Review |
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| Mendeliome v0.3318 | ABCA2 |
Zornitza Stark gene: ABCA2 was added gene: ABCA2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799 Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808 Review for gene: ABCA2 was set to GREEN Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals). Sources: Expert Review |
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| Mendeliome v0.3315 | HERC2 | Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3310 | TTI1 | Zornitza Stark Mode of inheritance for gene: TTI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3308 | SGMS2 |
Bryony Thompson gene: SGMS2 was added gene: SGMS2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SGMS2 were set to 30779713; 32028018 Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550 Review for gene: SGMS2 was set to GREEN Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum. Sources: Expert list |
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| Mendeliome v0.3305 | AKR1C4 | Zornitza Stark Mode of inheritance for gene: AKR1C4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3301 | PIP5K1C | Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3297 | ERBB3 | Zornitza Stark Mode of inheritance for gene: ERBB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3293 | DPM2 | Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3290 | C17orf62 | Zornitza Stark Tag new gene name tag was added to gene: C17orf62. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3288 | DYSF | Zornitza Stark Mode of inheritance for gene: DYSF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3285 | NEB | Zornitza Stark Mode of inheritance for gene: NEB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3282 | MRPS34 | Zornitza Stark Mode of inheritance for gene: MRPS34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3279 | GLS | Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3276 | PYCR1 | Seb Lunke Mode of inheritance for gene: PYCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3273 | PIGY | Zornitza Stark Mode of inheritance for gene: PIGY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3269 | MTMR14 | Zornitza Stark Mode of inheritance for gene: MTMR14 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3268 | P4HA1 |
Zornitza Stark gene: P4HA1 was added gene: P4HA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: P4HA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: P4HA1 were set to 28419360 Phenotypes for gene: P4HA1 were set to Joint hypermobility; Contractures; Hypotonia; Mild skeletal dysplasia without bone fragility; High myopia Review for gene: P4HA1 was set to RED Added comment: Single family reported with two affected individuals. Sources: Expert list |
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| Mendeliome v0.3266 | GGPS1 |
Zornitza Stark gene: GGPS1 was added gene: GGPS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GGPS1 were set to 32403198 Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency Review for gene: GGPS1 was set to GREEN Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality. Sources: Literature |
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| Mendeliome v0.3264 | DNMBP |
Seb Lunke gene: DNMBP was added gene: DNMBP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNMBP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNMBP were set to 30290152 Phenotypes for gene: DNMBP were set to congenital cataract Review for gene: DNMBP was set to GREEN gene: DNMBP was marked as current diagnostic Added comment: Multiple individuals from three independent large consanguineous families with bilateral infantile cataracts. Seperate hom nonsense variants. Sources: Literature |
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| Mendeliome v0.3263 | CRYGA |
Zornitza Stark gene: CRYGA was added gene: CRYGA was added to Mendeliome. Sources: Expert list refuted tags were added to gene: CRYGA. Mode of inheritance for gene: CRYGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CRYGA were set to 30450742; 28839118 Phenotypes for gene: CRYGA were set to Cataract Review for gene: CRYGA was set to RED Added comment: Reported as potentially disease causing in multiple individuals from two seperate families, but in both cases variant is present in the general population (20 Hets for one variant, >1000 hets and 9 homs in other variant) Sources: Expert list |
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| Mendeliome v0.3262 | AKR1E2 |
Zornitza Stark gene: AKR1E2 was added gene: AKR1E2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AKR1E2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AKR1E2 were set to 26622071 Phenotypes for gene: AKR1E2 were set to congenital cataracts Review for gene: AKR1E2 was set to RED Added comment: Same family with homozygous canonical splice variants and 3 cases of congenital cataract described in 2012 (original) and 2015 (review). No other descriptions since. Sources: Expert list |
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| Mendeliome v0.3259 | ADAMTSL4 | Zornitza Stark Mode of inheritance for gene: ADAMTSL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3258 | ADAMTSL4 | Zornitza Stark Tag founder tag was added to gene: ADAMTSL4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3256 | HIST1H4C | Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3253 | SFTPA1 | Zornitza Stark Mode of inheritance for gene: SFTPA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3250 | CFAP74 |
Zornitza Stark gene: CFAP74 was added gene: CFAP74 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP74 were set to 32555313 Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility Review for gene: CFAP74 was set to AMBER Added comment: Two unrelated individuals with compound het missense variants reported. Sources: Literature |
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| Mendeliome v0.3248 | ASPRV1 |
Ee Ming Wong gene: ASPRV1 was added gene: ASPRV1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ASPRV1 were set to PMID: 32516568 Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis Review for gene: ASPRV1 was set to GREEN gene: ASPRV1 was marked as current diagnostic Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds -mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing Sources: Literature |
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| Mendeliome v0.3244 | LGR4 | Zornitza Stark Mode of inheritance for gene: LGR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3242 | SREBF1 |
Paul De Fazio gene: SREBF1 was added gene: SREBF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SREBF1 were set to 32497488 Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome Review for gene: SREBF1 was set to GREEN gene: SREBF1 was marked as current diagnostic Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples. Sources: Literature |
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| Mendeliome v0.3241 | BTG4 |
Ain Roesley gene: BTG4 was added gene: BTG4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BTG4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BTG4 were set to PMID: 32502391 Phenotypes for gene: BTG4 were set to Zygotic cleavage failure (ZCF) Penetrance for gene: BTG4 were set to unknown Added comment: PMID: 32502391 - 4 affecteds from 4 families including 3 consanguineous families. 3 PTVs + 1 splice. - in vitro assays in HELA cells showed all PTVs had complete loss of protein. The missense variant had abolished interaction with CNOT7 - In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals, which provides a mechanistic explanation for the phenotype of ZCF Sources: Literature |
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| Mendeliome v0.3240 | KIAA1217 |
Zornitza Stark gene: KIAA1217 was added gene: KIAA1217 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIAA1217 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIAA1217 were set to 32369272 Phenotypes for gene: KIAA1217 were set to Vertebral anomalies, syndromic and non-syndromic Review for gene: KIAA1217 was set to AMBER Added comment: 10 families reported, however note only 3 of the variants were absent from gnomad, inheritance not reported, most variants are missense. Sources: Literature |
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| Mendeliome v0.3239 | RAP1GDS1 |
Zornitza Stark gene: RAP1GDS1 was added gene: RAP1GDS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAP1GDS1 were set to 32431071 Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features Review for gene: RAP1GDS1 was set to AMBER Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected. Sources: Literature |
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| Mendeliome v0.3236 | HOXD10 | Zornitza Stark Mode of inheritance for gene: HOXD10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3232 | ADPRHL2 | Zornitza Stark Mode of inheritance for gene: ADPRHL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3230 | GPR161 |
Zornitza Stark gene: GPR161 was added gene: GPR161 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GPR161 were set to 31609649 Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma Review for gene: GPR161 was set to GREEN Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue. Sources: Literature |
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| Mendeliome v0.3227 | SETD1B | Zornitza Stark Mode of inheritance for gene: SETD1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3225 | ARF1 |
Zornitza Stark gene: ARF1 was added gene: ARF1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARF1 were set to 28868155 Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185 Review for gene: ARF1 was set to GREEN Added comment: Three unrelated individuals reported with de novo missense in this gene. Sources: Expert list |
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| Mendeliome v0.3222 | MRAS |
Zornitza Stark gene: MRAS was added gene: MRAS was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MRAS were set to 28289718 Phenotypes for gene: MRAS were set to Noonan syndrome Review for gene: MRAS was set to AMBER Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen. Sources: Expert list |
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| Mendeliome v0.3219 | A2ML1 | Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3216 | NRG1 |
Bryony Thompson gene: NRG1 was added gene: NRG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NRG1 were set to 22574178; 21706185; 28190554 Phenotypes for gene: NRG1 were set to Hirschsprung disease Review for gene: NRG1 was set to AMBER Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease. Sources: Expert list |
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| Mendeliome v0.3213 | FLRT3 | Zornitza Stark Mode of inheritance for gene: FLRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3203 | RAD21 | Zornitza Stark Mode of inheritance for gene: RAD21 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3202 | CAPZA2 |
Eleanor Williams gene: CAPZA2 was added gene: CAPZA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CAPZA2 were set to 32338762 Phenotypes for gene: CAPZA2 were set to intellectual disability Review for gene: CAPZA2 was set to AMBER Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles. Sources: Literature |
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| Mendeliome v0.3202 | PPP3R1 |
Eleanor Williams gene: PPP3R1 was added gene: PPP3R1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PPP3R1 were set to 32337552; 19159392 Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654 Review for gene: PPP3R1 was set to RED Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members. Sources: Literature |
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| Mendeliome v0.3202 | PLEK |
Eleanor Williams gene: PLEK was added gene: PLEK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PLEK were set to 32337552; 19159392 Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654 Review for gene: PLEK was set to RED Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members. Sources: Literature |
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| Mendeliome v0.3202 | CNRIP1 |
Eleanor Williams gene: CNRIP1 was added gene: CNRIP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CNRIP1 were set to 32337552; 19159392 Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654 Review for gene: CNRIP1 was set to RED Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members. Sources: Literature |
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| Mendeliome v0.3202 | CCDC32 |
Eleanor Williams gene: CCDC32 was added gene: CCDC32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC32 were set to 32307552 Phenotypes for gene: CCDC32 were set to craniofacial, cardiac and neurodevelopmental anomalies Review for gene: CCDC32 was set to AMBER Added comment: PMID: 32307552 - Harel et al 2020 - reports 2 unrelated consanguineous families with probands with homozygous frameshift variants in CCDC32. Parents are heterozygous. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development. Sources: Literature |
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| Mendeliome v0.3200 | SKIV2L | Zornitza Stark Mode of inheritance for gene: SKIV2L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3198 | NLRP5 |
Zornitza Stark gene: NLRP5 was added gene: NLRP5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NLRP5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238 Phenotypes for gene: NLRP5 were set to Early embryonic arrest Review for gene: NLRP5 was set to AMBER Added comment: At least two families reported. Sources: Literature |
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| Mendeliome v0.3196 | EXOC7 |
Zornitza Stark gene: EXOC7 was added gene: EXOC7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC7 were set to 32103185 Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly Review for gene: EXOC7 was set to GREEN Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration. Sources: Literature |
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| Mendeliome v0.3195 | HNRNPH1 |
Zornitza Stark gene: HNRNPH1 was added gene: HNRNPH1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPH1 were set to 32335897; 29938792 Phenotypes for gene: HNRNPH1 were set to HNRNPH1‐related syndromic intellectual disability Review for gene: HNRNPH1 was set to GREEN Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant. 2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo. Sources: Literature |
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| Mendeliome v0.3194 | PDCD6IP |
Zornitza Stark gene: PDCD6IP was added gene: PDCD6IP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDCD6IP were set to 32286682 Phenotypes for gene: PDCD6IP were set to Microcephaly; intellectual disability Review for gene: PDCD6IP was set to AMBER Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies. Sources: Literature |
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| Mendeliome v0.3192 | NME5 |
Zornitza Stark gene: NME5 was added gene: NME5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NME5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NME5 were set to 32185794 Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia Review for gene: NME5 was set to AMBER Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy. Sources: Literature |
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| Mendeliome v0.3189 | EMILIN1 |
Naomi Baker gene: EMILIN1 was added gene: EMILIN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740. Phenotypes for gene: EMILIN1 were set to peripheral neuropathy Penetrance for gene: EMILIN1 were set to unknown Review for gene: EMILIN1 was set to AMBER Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein. Sources: Literature |
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| Mendeliome v0.3188 | ADAMTS3 |
Zornitza Stark gene: ADAMTS3 was added gene: ADAMTS3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS3 were set to 28985353; 30450763 Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154) Review for gene: ADAMTS3 was set to GREEN Added comment: Two families reported, supportive functional data. Sources: Expert list |
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| Mendeliome v0.3185 | MCM3AP | Eleanor Williams changed review comment from: PMID: 32202298 - Woldegebriel et al - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; to: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3185 | SP6 |
Eleanor Williams gene: SP6 was added gene: SP6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574 Phenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta Review for gene: SP6 was set to AMBER Added comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 ) Sources: Literature |
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| Mendeliome v0.3183 | MYH8 | Zornitza Stark Mode of inheritance for gene: MYH8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3182 | CACNB1 |
Zornitza Stark gene: CACNB1 was added gene: CACNB1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CACNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769 Phenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility Added comment: A single heterozygous case with a positive IVCT muscle biopsy has been reported with p.Val156Ala. The European non-Finnish allele frequency in gnomAD v2.1 is 0.001146 (148/129,118 alleles), which is higher than the expected population frequency for dominantly inherited malignant hyperthermia (0.1%). Additionally, functional assays of this variant, suggest it would only significantly affect function in the homozygous state (suggesting a recessive condition). Sources: Expert list |
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| Mendeliome v0.3179 | GATA6 | Zornitza Stark Mode of pathogenicity for gene: GATA6 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3178 | GATA6 | Zornitza Stark Mode of inheritance for gene: GATA6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3174 | TSHZ1 | Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3171 | TSHZ1 | Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3168 | ZBTB18 | Zornitza Stark Mode of pathogenicity for gene: ZBTB18 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3167 | ZBTB18 | Zornitza Stark Mode of inheritance for gene: ZBTB18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3165 | ESR2 |
Bryony Thompson gene: ESR2 was added gene: ESR2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ESR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Mendeliome v0.3161 | SETD2 | Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3158 | UBE2A | Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3156 | AXL |
Bryony Thompson gene: AXL was added gene: AXL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AXL were set to 18787040; 24476074 Phenotypes for gene: AXL were set to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism Review for gene: AXL was set to AMBER Added comment: Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P. Sources: Literature |
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| Mendeliome v0.3153 | GANAB | Zornitza Stark Mode of inheritance for gene: GANAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3150 | GOLGA2 |
Elena Savva gene: GOLGA2 was added gene: GOLGA2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501 Phenotypes for gene: GOLGA2 were set to Nueromuscular disorder Review for gene: GOLGA2 was set to GREEN Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC. Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression. PMID: 26742501 - One infant with a homozygous PTC. Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization. Summary: 2 patients + animal model Sources: Expert list |
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| Mendeliome v0.3145 | PHOX2A | Zornitza Stark Mode of inheritance for gene: PHOX2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3138 | ANKRD1 | Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3134 | CALR3 | Zornitza Stark Mode of inheritance for gene: CALR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3132 | CALR3 | Zornitza Stark Tag refuted tag was added to gene: CALR3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3130 | ALPK3 | Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3127 | HSF4 | Zornitza Stark Mode of inheritance for gene: HSF4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3125 | FITM2 |
Bryony Thompson gene: FITM2 was added gene: FITM2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FITM2 were set to 28067622; 30214770; 30288795 Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness Review for gene: FITM2 was set to GREEN Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model. Sources: Expert list |
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| Mendeliome v0.3121 | CHD1L | Zornitza Stark Mode of inheritance for gene: CHD1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3119 | CHD1L | Zornitza Stark Tag disputed tag was added to gene: CHD1L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3117 | NEXMIF | Zornitza Stark Mode of inheritance for gene: NEXMIF was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3115 | MEF2C | Zornitza Stark Mode of inheritance for gene: MEF2C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3112 | KDM6A | Zornitza Stark Mode of inheritance for gene: KDM6A was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3110 | STAG3 |
Bryony Thompson gene: STAG3 was added gene: STAG3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STAG3 were set to 24597867; 26059840; 31803224; 31363903 Phenotypes for gene: STAG3 were set to Premature ovarian failure 8 MIM#615723 Review for gene: STAG3 was set to GREEN Added comment: At least four unrelated families with ovarian failure and a supporting null mouse model. Sources: Expert list |
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| Mendeliome v0.3108 | SOHLH1 |
Bryony Thompson gene: SOHLH1 was added gene: SOHLH1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SOHLH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SOHLH1 were set to 25774885; 16690745; 31042289; 20506135; 28718531 Phenotypes for gene: SOHLH1 were set to Ovarian dysgenesis 5 MIM#617690; Spermatogenic failure 32 MIM#618115 Review for gene: SOHLH1 was set to GREEN Added comment: Women in 3 unrelated families with ovarian dysgenesis and homozygous variants, and a supporting null mouse model. At least 4 males with heterozygous variants and spermatogenic failure. Sources: Expert list |
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| Mendeliome v0.3106 | HFM1 |
Bryony Thompson gene: HFM1 was added gene: HFM1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: HFM1 were set to 23555294; 24597873; 31279343 Phenotypes for gene: HFM1 were set to Premature ovarian failure 9 MIM#615724 Review for gene: HFM1 was set to GREEN Added comment: Three cases from 2 unrelated families with compound heterozygous variants, and a single family with a heterozygous variant have been reported with ovarian failure. There is also a supporting null mouse model. Sources: Expert list |
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| Mendeliome v0.3103 | NEK9 | Zornitza Stark Mode of inheritance for gene: NEK9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3099 | MSTN | Zornitza Stark Mode of inheritance for gene: MSTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3095 | HSPB8 | Zornitza Stark Mode of inheritance for gene: HSPB8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3092 | AMPD1 | Zornitza Stark Mode of inheritance for gene: AMPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3090 | AMPD1 | Zornitza Stark Tag disputed tag was added to gene: AMPD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3088 | DCAF8 |
Bryony Thompson gene: DCAF8 was added gene: DCAF8 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DCAF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DCAF8 were set to 24500646 Phenotypes for gene: DCAF8 were set to Giant axonal neuropathy 2, autosomal dominant MIM#610100 Review for gene: DCAF8 was set to AMBER Added comment: A single large family segregating a missense variant and in vitro functional assays demonstrating the variant reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function Sources: Expert list |
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| Mendeliome v0.3086 | ARL6IP1 |
Bryony Thompson gene: ARL6IP1 was added gene: ARL6IP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARL6IP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARL6IP1 were set to 24482476; 31272422; 30980493; 28471035 Phenotypes for gene: ARL6IP1 were set to Spastic paraplegia 61, autosomal recessive MIM#615685 Review for gene: ARL6IP1 was set to GREEN gene: ARL6IP1 was marked as current diagnostic Added comment: At least 4 families reported with paediatric onset complicated spastic paraplegia and neuropathy. Supporting zebrafish model. Sources: Expert list |
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| Mendeliome v0.3085 | RFC1 | Bryony Thompson Tag STR tag was added to gene: RFC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3084 | PMP2 |
Bryony Thompson gene: PMP2 was added gene: PMP2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PMP2 were set to 26257172; 26828946; 27009151 Phenotypes for gene: PMP2 were set to Charcot-Marie-Tooth disease, demyelinating, type 1G MIM#618279 Review for gene: PMP2 was set to GREEN Added comment: 4 unrelated families reported with missense variants, with supporting transgenic mouse and null zebrafish models. Sources: Expert list |
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| Mendeliome v0.3082 | HPRT1 | Zornitza Stark Mode of inheritance for gene: HPRT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3079 | ASTN2 | Zornitza Stark Mode of inheritance for gene: ASTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3076 | SI | Zornitza Stark Mode of inheritance for gene: SI was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3075 | SV2B |
Seb Lunke gene: SV2B was added gene: SV2B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SV2B was set to Unknown Publications for gene: SV2B were set to 23617838; 23937191 Phenotypes for gene: SV2B were set to seizures Review for gene: SV2B was set to RED Added comment: Multiply described in Epilepsy studies investigating role of SV2 gene family, however no patients directly attributed to variants in this gene and mouse models indicate viability without seizures. Sources: Literature Sources: Literature |
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| Mendeliome v0.3073 | RYR3 |
Zornitza Stark gene: RYR3 was added gene: RYR3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RYR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RYR3 were set to 29498452; 32451403; 31230720 Phenotypes for gene: RYR3 were set to Nemaline myopathy; fetal akinesia; arthrogryposis Review for gene: RYR3 was set to AMBER Added comment: One family reported with nemaline myopathy and other cases reported as part of large fetal akinesia/arthrogryposis discovery cohorts reporting multiple novel gene candidates. Sources: Expert list |
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| Mendeliome v0.3070 | SCN3A | Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3069 | SCN3A | Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3063 | PLAG1 | Zornitza Stark Mode of inheritance for gene: PLAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3059 | NEFH | Zornitza Stark Mode of pathogenicity for gene: NEFH was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3058 | NEFH | Zornitza Stark Mode of inheritance for gene: NEFH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3055 | SLC6A1 | Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3052 | GATM | Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3051 | TRIM69 |
Zornitza Stark gene: TRIM69 was added gene: TRIM69 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TRIM69 were set to 22105173 Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis Review for gene: TRIM69 was set to RED Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described. Sources: Expert list |
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| Mendeliome v0.3050 | LIMS2 |
Zornitza Stark gene: LIMS2 was added gene: LIMS2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: LIMS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIMS2 were set to 25589244; 16317048 Phenotypes for gene: LIMS2 were set to Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue MIM#616827 Review for gene: LIMS2 was set to RED Added comment: Only one family reported and Pinch2 -/- mice were viable and fertile with no apparent phenotype. Sources: Expert list |
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| Mendeliome v0.3048 | PSMB1 |
Zornitza Stark gene: PSMB1 was added gene: PSMB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMB1 were set to 32129449 Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly Review for gene: PSMB1 was set to AMBER Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model. Sources: Literature |
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| Mendeliome v0.3045 | SLC12A6 | Zornitza Stark Mode of inheritance for gene: SLC12A6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3042 | EWSR1 | Seb Lunke Mode of inheritance for gene: EWSR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3038 | C16orf62 | Zornitza Stark Tag new gene name tag was added to gene: C16orf62. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3037 | C16orf62 |
Zornitza Stark gene: C16orf62 was added gene: C16orf62 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C16orf62 were set to 25434475 Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome Review for gene: C16orf62 was set to AMBER Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475). Sources: Expert list |
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| Mendeliome v0.3034 | RHOBTB2 | Zornitza Stark Mode of pathogenicity for gene: RHOBTB2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3033 | RHOBTB2 | Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3030 | PPP1CB | Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3028 | NUP88 |
Zornitza Stark gene: NUP88 was added gene: NUP88 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP88 were set to 30543681 Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393 Review for gene: NUP88 was set to GREEN Added comment: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model. Sources: Literature |
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| Mendeliome v0.3025 | SMO | Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3024 | RBL2 |
Zornitza Stark gene: RBL2 was added gene: RBL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RBL2 were set to 32105419; 9806916 Phenotypes for gene: RBL2 were set to Intellectual disability Review for gene: RBL2 was set to RED Added comment: Single family reported with pair of affected siblings. Supportive mouse model. Sources: Literature |
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| Mendeliome v0.3022 | GRM7 |
Zornitza Stark gene: GRM7 was added gene: GRM7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GRM7 were set to 32286009; 32248644 Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay Review for gene: GRM7 was set to GREEN Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model. Sources: Literature |
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| Mendeliome v0.3019 | PYGM | Zornitza Stark Mode of inheritance for gene: PYGM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3017 | PERP |
Zornitza Stark gene: PERP was added gene: PERP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PERP were set to 31898316 Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet Review for gene: PERP was set to AMBER Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible. Sources: Literature |
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| Mendeliome v0.3015 | ADCY6 |
Zornitza Stark gene: ADCY6 was added gene: ADCY6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADCY6 were set to 24319099; 26257172; 31846058 Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8, OMIM # 616287 Review for gene: ADCY6 was set to GREEN Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies. Sources: Literature |
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| Mendeliome v0.3014 | DSCR3 |
Zornitza Stark gene: DSCR3 was added gene: DSCR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DSCR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DSCR3 were set to 31845315 Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet Review for gene: DSCR3 was set to RED Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals. Sources: Literature |
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| Mendeliome v0.3013 | LEF1 |
Zornitza Stark gene: LEF1 was added gene: LEF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LEF1 were set to 32022899 Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet Review for gene: LEF1 was set to RED Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human. Sources: Literature |
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| Mendeliome v0.3010 | OTUD7A |
Zornitza Stark gene: OTUD7A was added gene: OTUD7A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OTUD7A were set to 31997314 Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet Review for gene: OTUD7A was set to RED Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies. Sources: Literature |
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| Mendeliome v0.3007 | GATAD2B | Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3003 | KMT2D | Zornitza Stark Mode of inheritance for gene: KMT2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3000 | COG4 | Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2997 | ARL13B | Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2994 | DNAL1 | Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2992 | DNAL1 | Zornitza Stark Tag founder tag was added to gene: DNAL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2990 | DNAH8 | Zornitza Stark Mode of inheritance for gene: DNAH8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2987 | TTC5 |
Zornitza Stark gene: TTC5 was added gene: TTC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC5 were set to 29302074; 32439809 Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system Review for gene: TTC5 was set to GREEN Added comment: Eleven individuals from seven families reported. Sources: Literature |
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| Mendeliome v0.2982 | DRC1 | Zornitza Stark Mode of inheritance for gene: DRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2981 | DRC1 | Zornitza Stark Tag SV/CNV tag was added to gene: DRC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2979 | TLL1 | Zornitza Stark Mode of inheritance for gene: TLL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2977 | HIST1H4J |
Zornitza Stark gene: HIST1H4J was added gene: HIST1H4J was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HIST1H4J were set to 31804630 Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features Review for gene: HIST1H4J was set to AMBER Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype Sources: Literature |
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| Mendeliome v0.2974 | MCIDAS | Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2968 | EFEMP1 | Zornitza Stark Mode of inheritance for gene: EFEMP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2965 | USP8 |
Bryony Thompson gene: USP8 was added gene: USP8 was added to Mendeliome. Sources: Expert list somatic tags were added to gene: USP8. Mode of inheritance for gene: USP8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: USP8 were set to 25675982; 24482476; 25485838; 25942478 Phenotypes for gene: USP8 were set to Pituitary adenoma 4, ACTH-secreting, somatic MIM#219090; hereditary spastic paraplegia Review for gene: USP8 was set to GREEN Added comment: Recurrent somatic gain of function missense variants in pituitary adenomas cause Cushing's disease. A single family reported with spastic paraplegia with a homozygous variant, and a zebrafish model with a movement disorder. Sources: Expert list |
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| Mendeliome v0.2962 | TRIM71 | Seb Lunke Mode of pathogenicity for gene: TRIM71 was changed from Other to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2959 | SCYL2 |
Zornitza Stark gene: SCYL2 was added gene: SCYL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCYL2 were set to 31960134; 26203146 Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome Review for gene: SCYL2 was set to AMBER Added comment: Two unrelated families reported with AMC, variable other features including microcephaly. Sources: Literature |
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| Mendeliome v0.2955 | VWA3B |
Bryony Thompson gene: VWA3B was added gene: VWA3B was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VWA3B were set to 26157035 Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948 Review for gene: VWA3B was set to AMBER Added comment: A homozygous missense variant was identified in 3 brothers from a single consanguineous Japanese family with autosomal recessive cerebellar ataxia. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability. Sources: Expert list |
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| Mendeliome v0.2952 | SLC12A2 | Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2950 | PLD3 |
Bryony Thompson gene: PLD3 was added gene: PLD3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PLD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLD3 were set to 29053796; 30312375; 30312384 Phenotypes for gene: PLD3 were set to Spinocerebellar ataxia 46 MIM#617770 Review for gene: PLD3 was set to AMBER Added comment: A heterozygous missense was identified in 8 affected members of a single family with spinocerebellar ataxia, and supporting in vitro functional assays. Sources: Expert list |
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| Mendeliome v0.2944 | POC5 |
Bryony Thompson gene: POC5 was added gene: POC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POC5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: POC5 were set to 25642776; 29272404 Phenotypes for gene: POC5 were set to Idiopathic scoliosis; retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis Review for gene: POC5 was set to GREEN Added comment: Three heterozygous missense variants identified in three families segregating with idiopathic scoliosis, and supporting zebrafish models for each of the missense variants. Also, one case reported with retinitis pigmentosa, short stature, microcephaly, and recurrent glomerulonephritis with a homozygous truncating variant and a supporting zebrafish model. Sources: Literature |
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| Mendeliome v0.2943 | KIF3B |
Paul De Fazio gene: KIF3B was added gene: KIF3B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly Review for gene: KIF3B was set to AMBER Added comment: 2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking. Sources: Literature |
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| Mendeliome v0.2943 | SPATA13 |
Ain Roesley gene: SPATA13 was added gene: SPATA13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPATA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPATA13 were set to PMID: 32339198 Phenotypes for gene: SPATA13 were set to primary angle-closure glaucoma Added comment: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp. Sources: Literature |
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| Mendeliome v0.2943 | SOX6 |
Paul De Fazio gene: SOX6 was added gene: SOX6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SOX6 were set to 32442410 Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature |
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| Mendeliome v0.2943 | CNP |
Kristin Rigbye gene: CNP was added gene: CNP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CNP were set to 32128616; 12590258 Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy Review for gene: CNP was set to AMBER Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling). Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts. Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family. Sources: Literature |
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| Mendeliome v0.2943 | TRIM71 |
Elena Savva gene: TRIM71 was added gene: TRIM71 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633 Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667 Mode of pathogenicity for gene: TRIM71 was set to Other Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child. PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism. Sources: Literature |
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| Mendeliome v0.2943 | RIMS2 |
Paul De Fazio gene: RIMS2 was added gene: RIMS2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RIMS2 were set to 32470375 Review for gene: RIMS2 was set to GREEN Added comment: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Sources: Literature |
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| Mendeliome v0.2942 | RBM7 |
Bryony Thompson gene: RBM7 was added gene: RBM7 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RBM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RBM7 were set to 27193168 Phenotypes for gene: RBM7 were set to SMA-like spinal motor neuropathy; dHMN/dSMA Review for gene: RBM7 was set to AMBER Added comment: Single case with a homozygote variant, with functional assays in patient fibroblasts. Also, supporting zebrafish model. Sources: Expert list |
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| Mendeliome v0.2940 | SORD |
Seb Lunke gene: SORD was added gene: SORD was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SORD were set to 32367058 Phenotypes for gene: SORD were set to isolated hereditary neuropathy Review for gene: SORD was set to GREEN gene: SORD was marked as current diagnostic Added comment: 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state Sources: Literature |
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| Mendeliome v0.2938 | KCNJ8 | Zornitza Stark Mode of inheritance for gene: KCNJ8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2936 | KCNJ8 | Zornitza Stark Tag disputed tag was added to gene: KCNJ8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2934 | KCNE3 | Zornitza Stark Mode of inheritance for gene: KCNE3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2932 | DNAH6 |
Elena Savva gene: DNAH6 was added gene: DNAH6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAH6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH6 were set to PMID: 26918822 Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia Review for gene: DNAH6 was set to AMBER Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width. Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1. Summary: 1 convincing patient with animal model Sources: Literature |
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| Mendeliome v0.2931 | XIST | Zornitza Stark Mode of inheritance for gene: XIST was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2924 | ANO5 | Zornitza Stark Mode of inheritance for gene: ANO5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2922 | CPT1B | Zornitza Stark Mode of inheritance for gene: CPT1B was changed from Unknown to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2916 | DNAJB11 | Zornitza Stark Mode of inheritance for gene: DNAJB11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2913 | GPR143 | Zornitza Stark Mode of inheritance for gene: GPR143 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2910 | ELP1 | Zornitza Stark Mode of inheritance for gene: ELP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2907 | SNRNP200 | Zornitza Stark Mode of inheritance for gene: SNRNP200 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2906 | SNRNP200 |
Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo |
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| Mendeliome v0.2906 | SNRNP200 |
Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo |
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| Mendeliome v0.2904 | ALOXE3 | Zornitza Stark Mode of inheritance for gene: ALOXE3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2900 | STK36 | Zornitza Stark Mode of inheritance for gene: STK36 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2896 | NME8 | Zornitza Stark Mode of inheritance for gene: NME8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2892 | TFAP2A | Zornitza Stark Mode of pathogenicity for gene: TFAP2A was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2891 | TFAP2A | Zornitza Stark Mode of inheritance for gene: TFAP2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2889 | ARL3 |
Bryony Thompson gene: ARL3 was added gene: ARL3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ARL3 were set to 30269812; 16565502; 26964041; 30932721 Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161; Retinitis pigmentosa 83 MIM#618173 Review for gene: ARL3 was set to GREEN Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina. Two unrelated families with retinitis pigmentosa segregating the same heterozygous missense variant (Y90C). Sources: Expert list |
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| Mendeliome v0.2882 | CEP19 |
Bryony Thompson gene: CEP19 was added gene: CEP19 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP19 were set to 29127258; 24268657 Phenotypes for gene: CEP19 were set to Morbid obesity and spermatogenic failure MIM#615703 Review for gene: CEP19 was set to AMBER Added comment: A consanguineous Arab family with morbid obesity and infertility with a homozygous predicted null variant, and a mouse model that recapitulates the phenotype. Another homozygous variant has been identified in a consanguineous Bardet Beidl syndrome. Sources: Literature |
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| Mendeliome v0.2880 | DALRD3 |
Zornitza Stark gene: DALRD3 was added gene: DALRD3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DALRD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DALRD3 were set to 32427860 Phenotypes for gene: DALRD3 were set to Epileptic encephalopathy Review for gene: DALRD3 was set to AMBER Added comment: Two individuals reported with same homozygous nonsense variant, functional data. Sources: Literature |
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| Mendeliome v0.2874 | KRAS | Zornitza Stark Mode of pathogenicity for gene: KRAS was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2873 | KRAS | Zornitza Stark Mode of inheritance for gene: KRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2871 | GAA | Zornitza Stark Mode of inheritance for gene: GAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2868 | HEXA | Zornitza Stark Mode of inheritance for gene: HEXA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2865 | DHX30 | Zornitza Stark Mode of inheritance for gene: DHX30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2862 | FAT1 | Zornitza Stark Mode of inheritance for gene: FAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2861 | FAT1 |
Ee Ming Wong changed review comment from: - 5 consanguineous families with homozygous frameshift mutations in FAN1 - FAN1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice - in human retinal pigment epithelium (RPE) cells, FAN1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation; to: - 5 consanguineous families with homozygous frameshift mutations in FAN1 - FAN1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice - in human retinal pigment epithelium (RPE) cells, FAN1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation |
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| Mendeliome v0.2859 | JARID2 |
Zornitza Stark gene: JARID2 was added gene: JARID2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JARID2 were set to 23294540 Phenotypes for gene: JARID2 were set to Intellectual disability Review for gene: JARID2 was set to AMBER Added comment: Emerging evidence that haploinsufficiency causes neurodevelopmental phenotypes, mostly based on CNV data to date. Sources: Expert Review |
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| Mendeliome v0.2855 | ADIPOR1 | Zornitza Stark Mode of inheritance for gene: ADIPOR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2851 | TRIP12 | Zornitza Stark Mode of inheritance for gene: TRIP12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2847 | CLCC1 |
Bryony Thompson gene: CLCC1 was added gene: CLCC1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CLCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLCC1 were set to 30157172 Phenotypes for gene: CLCC1 were set to Retinitis pigmentosa 32 Review for gene: CLCC1 was set to AMBER Added comment: A presumptive Pakastani founder mutation (c.75C>A, p.D25E) was identified in 8 consanguineous arRP families. A knockout zebrafish model and a Clcc1 +/- mouse model had a supporting retinal phenotype. Sources: Expert list |
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| Mendeliome v0.2844 | B9D1 | Zornitza Stark Mode of inheritance for gene: B9D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2842 | B9D1 |
Zornitza Stark changed review comment from: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype. Sources: Expert list; to: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. This latter individual had a splice site variant and a deletion. Splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant i dont see the results are usable PMID: 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant. |
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| Mendeliome v0.2840 | BBIP1 | Zornitza Stark Mode of inheritance for gene: BBIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2836 | PACS1 | Zornitza Stark Mode of inheritance for gene: PACS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2832 | STARD7 |
Zornitza Stark gene: STARD7 was added gene: STARD7 was added to Mendeliome. Sources: Expert list STR tags were added to gene: STARD7. Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: STARD7 were set to 11701600; 24114805; 31664034 Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876 Mode of pathogenicity for gene: STARD7 was set to Other Review for gene: STARD7 was set to GREEN Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene. Sources: Expert list |
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| Mendeliome v0.2828 | DHCR7 | Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2825 | PDXK |
Russell Gear gene: PDXK was added gene: PDXK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDXK were set to (PMID: 31187503) Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy Review for gene: PDXK was set to RED Added comment: Currently two unrelated families with axonal polyneuropathy and optic atrophy described in the same paper, with bi-allelic PDXK pathogenic variants. Functional work in the same paper includes work on patient derived fibroblasts, measurement of an axonal damage biomarker (NFL protein), and response to PLP supplementation treatment. Need one further unrelated family to upgrade to green? Sources: Literature |
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| Mendeliome v0.2823 | NDP | Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2820 | TMEM107 | Zornitza Stark Mode of inheritance for gene: TMEM107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2817 | ALPL | Zornitza Stark Mode of pathogenicity for gene: ALPL was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2816 | ALPL | Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2814 | LRRC56 |
Elena Savva gene: LRRC56 was added gene: LRRC56 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC56 were set to PMID: 30388400 Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254 Added comment: PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient. 3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus Sources: Expert list |
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| Mendeliome v0.2812 | MOGS | Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2809 | TCF7L1 | Zornitza Stark Mode of inheritance for gene: TCF7L1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2806 | GFI1B |
Bryony Thompson gene: GFI1B was added gene: GFI1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872 Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900 Review for gene: GFI1B was set to GREEN Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development. Sources: Literature |
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| Mendeliome v0.2803 | PRKD1 | Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2800 | NODAL | Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2798 | NODAL | Zornitza Stark Tag disputed tag was added to gene: NODAL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2796 | PIH1D3 | Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2793 | COL10A1 | Zornitza Stark Mode of inheritance for gene: COL10A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2791 | CEP112 |
Bryony Thompson gene: CEP112 was added gene: CEP112 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP112 were set to 31654588 Phenotypes for gene: CEP112 were set to Acephalic spermatozoa; infertility Review for gene: CEP112 was set to AMBER Added comment: Two unrelated cases reported with acephalic spermatozoa, one case with a homozygous nonsense variant and the other case with biallelic missense variants. CEP112 expression was significantly reduced in one of the cases, suggesting loss of function as a mechanism of disease. Sources: Literature |
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| Mendeliome v0.2790 | KPNA7 |
Alison Yeung gene: KPNA7 was added gene: KPNA7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KPNA7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KPNA7 were set to 24045845; 32179771 Phenotypes for gene: KPNA7 were set to Epilepsy; intellectual disability Review for gene: KPNA7 was set to RED Added comment: Single family with two siblings Sources: Literature |
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| Mendeliome v0.2788 | NR4A2 |
Zornitza Stark gene: NR4A2 was added gene: NR4A2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NR4A2 were set to 31428396; 30504930; 29770430; 12756136; 9092472 Phenotypes for gene: NR4A2 were set to Intellectual disability; epilepsy Review for gene: NR4A2 was set to GREEN Added comment: Over ten individuals reported with mono-allelic variants in this gene and neurodevelopmental phenotypes. Link with dementia/Parkinson's disease disputed. Sources: Literature |
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| Mendeliome v0.2786 | TOMM70 |
Zornitza Stark gene: TOMM70 was added gene: TOMM70 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TOMM70 were set to 31907385; 32356556 Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis, developmental delay; White matter abnormalities, developmental delay, regression, movement disorder Review for gene: TOMM70 was set to AMBER Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria. Bi-allelic disease: one individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments. Monoallelic disease: de novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data. Sources: Expert list |
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| Mendeliome v0.2782 | CUL3 | Zornitza Stark Mode of inheritance for gene: CUL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2779 | EGR2 | Zornitza Stark Mode of pathogenicity for gene: EGR2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2778 | EGR2 | Zornitza Stark Mode of inheritance for gene: EGR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2775 | GAS2L2 | Zornitza Stark Mode of inheritance for gene: GAS2L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2771 | KLB |
Zornitza Stark gene: KLB was added gene: KLB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLB were set to 28754744 Review for gene: KLB was set to GREEN Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Functional analysis showed decreased activity in response to FGF21 and FGF8. KLB is an obligate coreceptor for FGF21 alongside FGFR1. Sources: Literature |
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| Mendeliome v0.2769 | NDNF |
Zornitza Stark gene: NDNF was added gene: NDNF was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NDNF were set to 31883645 Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH) Review for gene: NDNF was set to GREEN Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models. Sources: Literature |
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| Mendeliome v0.2767 | UGDH |
Zornitza Stark gene: UGDH was added gene: UGDH was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGDH were set to 32001716 Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792 Review for gene: UGDH was set to GREEN Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode. UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate). Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors Sources: Literature |
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| Mendeliome v0.2764 | YIF1B |
Zornitza Stark gene: YIF1B was added gene: YIF1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to 32006098; 26077767 Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement Review for gene: YIF1B was set to GREEN Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. Sources: Literature |
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| Mendeliome v0.2761 | TNRC6B | Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2759 | TNRC6B | Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2758 | CDC42BPB |
Zornitza Stark gene: CDC42BPB was added gene: CDC42BPB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDC42BPB were set to 32031333 Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality Review for gene: CDC42BPB was set to GREEN Added comment: 14 individuals with missense and loss-of-function CDC42BPB variants reported. Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc. Most variants occurred as de novo events (11/14) while inheritance was not available for few (3/14). Sources: Literature |
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| Mendeliome v0.2755 | DNAJB13 | Zornitza Stark Mode of inheritance for gene: DNAJB13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2751 | CFC1 | Zornitza Stark Mode of inheritance for gene: CFC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2748 | CFAP53 | Zornitza Stark Mode of inheritance for gene: CFAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2745 | TTC25 | Zornitza Stark Mode of inheritance for gene: TTC25 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2742 | CFAP43 |
Elena Savva gene: CFAP43 was added gene: CFAP43 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP43 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551 Phenotypes for gene: CFAP43 were set to Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592 Added comment: aka WDR96 PMID: 31884020 - animal models (mouse, frog) demonstrate the protein localizes in ciliary axoneme and is involved in MOTILE cilia movement. LOF CFAP43 caused mucus acucmulation in airways, impaired spermatogenesis and hydrocephalus. PMID: 28552195 - 3x chet (bilallelic PTCs or chet PTC/missense) with abnormal sperm motility. Null mouse models were also infertile. PMID: 31004071 - one family with a heterozygous nonsense and AD inheritance of late onset hydrocephaly (checked in Mutalyzer, variant is NMD predicted). Abnormal cilia observed from mucosa sample. Null mice also show abnormal sperm and dilation of brain ventricles. PMID: 29449551 - reports an additional 10 patients with either homozygous PTCs or chet PTC/missense who were infertile with flagella defects Summary: single report of AD hydrocephaly Sources: Literature |
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| Mendeliome v0.2740 | MYLK2 | Zornitza Stark Mode of inheritance for gene: MYLK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2736 | CDX2 | Zornitza Stark Mode of inheritance for gene: CDX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2732 | TAPT1 | Zornitza Stark Mode of inheritance for gene: TAPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2729 | CCDC28B | Zornitza Stark edited their review of gene: CCDC28B: Added comment: PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.; Changed rating: AMBER; Changed publications: 32139166; Changed phenotypes: {Bardet-Biedl syndrome 1, modifier of}, MIM#209900, Joubert syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2729 | C21orf59 | Zornitza Stark Tag founder tag was added to gene: C21orf59. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2729 | C11orf70 | Zornitza Stark Tag new gene name tag was added to gene: C11orf70. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2727 | C11orf70 | Zornitza Stark Mode of inheritance for gene: C11orf70 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2724 | ARMC9 | Zornitza Stark Mode of inheritance for gene: ARMC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2720 | ARMC4 | Zornitza Stark Mode of inheritance for gene: ARMC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2717 | ACVR2B | Zornitza Stark Mode of inheritance for gene: ACVR2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2713 | NID1 | Zornitza Stark Mode of inheritance for gene: NID1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2710 | DARS | Zornitza Stark Mode of inheritance for gene: DARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2709 | DARS | Zornitza Stark Tag new gene name tag was added to gene: DARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2709 | CCDC65 | Zornitza Stark Tag founder tag was added to gene: CCDC65. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2707 | CCDC65 | Zornitza Stark Mode of inheritance for gene: CCDC65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2704 | C21orf59 | Zornitza Stark Mode of inheritance for gene: C21orf59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2703 | C21orf59 | Zornitza Stark Tag new gene name tag was added to gene: C21orf59. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2701 | WISP3 | Zornitza Stark Mode of inheritance for gene: WISP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2700 | WISP3 | Zornitza Stark Tag new gene name tag was added to gene: WISP3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2698 | ATP5E | Zornitza Stark Mode of inheritance for gene: ATP5E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2696 | ATP5E | Zornitza Stark Tag new gene name tag was added to gene: ATP5E. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2694 | ATP5D | Zornitza Stark Mode of inheritance for gene: ATP5D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2693 | ATP5D | Zornitza Stark Tag new gene name tag was added to gene: ATP5D. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2692 | ATP5A1 | Zornitza Stark Tag new gene name tag was added to gene: ATP5A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2691 | ATP5A1 | Zornitza Stark Mode of inheritance for gene: ATP5A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2687 | GLDC | Zornitza Stark Mode of inheritance for gene: GLDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2686 | TNK2 | Zornitza Stark Mode of inheritance for gene: TNK2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2683 | TNK2 | Zornitza Stark Mode of inheritance for gene: TNK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2681 | MAN2B2 |
Zornitza Stark gene: MAN2B2 was added gene: MAN2B2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAN2B2 were set to 31775018 Phenotypes for gene: MAN2B2 were set to Congenital disorder of glycosylation; immunodeficiency Review for gene: MAN2B2 was set to RED Added comment: Single individual reported. Sources: Literature |
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| Mendeliome v0.2678 | RIPK1 | Zornitza Stark Mode of inheritance for gene: RIPK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2676 | PIK3CG |
Zornitza Stark gene: PIK3CG was added gene: PIK3CG was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PIK3CG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3CG were set to 32001535; 31554793 Phenotypes for gene: PIK3CG were set to Immune dysregulation; HLH-like; childhood-onset antibody defects; cytopenias; T lymphocytic pneumonitis and colitis Review for gene: PIK3CG was set to GREEN Added comment: Two individuals with complex immunological phenotypes reported and a mouse model. Sources: Literature |
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| Mendeliome v0.2674 | RC3H1 |
Zornitza Stark gene: RC3H1 was added gene: RC3H1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RC3H1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RC3H1 were set to 31636267 Phenotypes for gene: RC3H1 were set to Relapsing HLH Review for gene: RC3H1 was set to RED Added comment: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data. Sources: Literature |
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| Mendeliome v0.2671 | IFNG | Zornitza Stark Mode of inheritance for gene: IFNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2669 | ITPKB |
Zornitza Stark gene: ITPKB was added gene: ITPKB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITPKB were set to 31987846 Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells Review for gene: ITPKB was set to RED Added comment: Single individual with homozygous bi-allelic LoF variant reported. Sources: Literature |
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| Mendeliome v0.2668 | PSMB10 |
Zornitza Stark gene: PSMB10 was added gene: PSMB10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMB10 were set to 31783057 Phenotypes for gene: PSMB10 were set to Autoinflammatory syndrome Review for gene: PSMB10 was set to RED Added comment: PSMB10 is part of the immunoproteasome, and other components cause auto inflammatory disorders. Single individual with homozygous missense variant reported. Sources: Literature |
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| Mendeliome v0.2666 | ABHD12 | Zornitza Stark Mode of inheritance for gene: ABHD12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2664 | AAAS | Zornitza Stark Mode of inheritance for gene: AAAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2659 | SNORA31 |
Zornitza Stark gene: SNORA31 was added gene: SNORA31 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SNORA31 were set to 31806906 Phenotypes for gene: SNORA31 were set to Susceptibility to HSV1 encephalitis Review for gene: SNORA31 was set to GREEN Added comment: Five unrelated individuals reported with rare missense variants in this gene, functional data to support susceptibility to herpes simplex encephalitis. Sources: Expert list |
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| Mendeliome v0.2656 | TCOF1 | Zornitza Stark Mode of inheritance for gene: TCOF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2655 | EMX2 | Zornitza Stark Tag disputed tag was added to gene: EMX2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2653 | EMX2 | Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2647 | CTSA | Zornitza Stark Mode of inheritance for gene: CTSA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2643 | PI4KA | Zornitza Stark Mode of inheritance for gene: PI4KA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2639 | CDK5 | Zornitza Stark Mode of inheritance for gene: CDK5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2636 | VPS51 |
Zornitza Stark gene: VPS51 was added gene: VPS51 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS51 were set to 30624672; 31207318 Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606 Review for gene: VPS51 was set to AMBER Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable. Sources: Expert list |
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| Mendeliome v0.2634 | CDK19 |
Zornitza Stark gene: CDK19 was added gene: CDK19 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDK19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDK19 were set to 32330417 Phenotypes for gene: CDK19 were set to Intellectual disability; epileptic encephalopathy Review for gene: CDK19 was set to GREEN Added comment: Three unrelated individuals with de novo missense variants reported, and intellectual disability/epileptic encephalopathy. Supportive functional data. Sources: Literature |
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| Mendeliome v0.2632 | MNS1 |
Zornitza Stark gene: MNS1 was added gene: MNS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MNS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MNS1 were set to 31534215; 30148830 Phenotypes for gene: MNS1 were set to Heterotaxy; male infertility Review for gene: MNS1 was set to GREEN Added comment: Eight families reported altogether, three LoF variants. Four Amish families share same homozygous founder variant, and some of the other reported families are consanguineous and share another founder variant. A reported female with a third variant, also had a homozygous variant in DNAH5 with a blended phenotype postulated. Sources: Literature |
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| Mendeliome v0.2630 | DHX37 |
Zornitza Stark gene: DHX37 was added gene: DHX37 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHX37 were set to 31337883; 31745530 Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS) Review for gene: DHX37 was set to GREEN Added comment: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies. Sources: Literature |
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| Mendeliome v0.2626 | RAMP2 |
Zornitza Stark gene: RAMP2 was added gene: RAMP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAMP2 were set to 31000793 Phenotypes for gene: RAMP2 were set to Primary open angle glaucoma Review for gene: RAMP2 was set to AMBER Added comment: Six variants identified in 16 of 4763 POAG patients from large cohorts; none identified in 10,953 control individuals. Some functional data. Sources: Literature |
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| Mendeliome v0.2625 | ALPK1 |
Zornitza Stark changed review comment from: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling. Sources: Literature; to: Three unrelated families reported with PFAPA phenotype. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling. Sources: Literature |
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| Mendeliome v0.2624 | MEPE |
Zornitza Stark gene: MEPE was added gene: MEPE was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MEPE were set to 30287925 Phenotypes for gene: MEPE were set to hereditary congenital facial paresis; otosclerosis Review for gene: MEPE was set to AMBER Added comment: Single four-generation family reported with variant in this gene segregating nonprogressive HCFP and mixed hearing loss (HL). Damaging variants (truncating/frameshift) found to be enriched in otosclerosis cohort (p = 0.0006–0.0060). Sources: Literature |
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| Mendeliome v0.2623 | PAICS |
Zornitza Stark gene: PAICS was added gene: PAICS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PAICS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAICS were set to 31600779 Phenotypes for gene: PAICS were set to Polyhydramnios; multiple congenital abnormalities Review for gene: PAICS was set to RED Added comment: Two sibs from single family reported with homozygous missense variant. Functional data to demonstrate effect on protein function. Sources: Literature |
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| Mendeliome v0.2620 | GALM |
Hazel Phillimore gene: GALM was added gene: GALM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to PMID: 30451973; 30910422 Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia Review for gene: GALM was set to GREEN Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422) Sources: Literature |
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| Mendeliome v0.2620 | POLR3GL |
Paul De Fazio gene: POLR3GL was added gene: POLR3GL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POLR3GL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3GL were set to 31089205; 31695177 Phenotypes for gene: POLR3GL were set to endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy Review for gene: POLR3GL was set to AMBER gene: POLR3GL was marked as current diagnostic Added comment: Biallelic canonical splice variants were identified in monozygotic twins and another individual with similar phenotypes from 2 unrelated families. Variants were inherited from carrier parents. RNA studies confirmed exon skipping occurs in all affected individuals. A separate study identified a homozygous nonsense variant in an individual with features of Neonatal progeroid syndrome/Wiedemann–Rautenstrauch syndrome. Quantitative PCR showed reduction in mRNA suggestive of NMD. Sources: Literature |
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| Mendeliome v0.2618 | TSPEAR | Zornitza Stark Mode of inheritance for gene: TSPEAR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2616 | PDGFRB | Zornitza Stark Mode of pathogenicity for gene: PDGFRB was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2614 | PDGFRB | Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2611 | TBL1Y |
Paul De Fazio gene: TBL1Y was added gene: TBL1Y was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TBL1Y was set to Other Publications for gene: TBL1Y were set to 30341416 Phenotypes for gene: TBL1Y were set to Hearing loss Review for gene: TBL1Y was set to RED gene: TBL1Y was marked as current diagnostic Added comment: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate. Sources: Literature |
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| Mendeliome v0.2610 | DGCR8 |
Chern Lim gene: DGCR8 was added gene: DGCR8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DGCR8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DGCR8 were set to 31805011 Phenotypes for gene: DGCR8 were set to Early-onset multinodular goiter and schwannomatosis Review for gene: DGCR8 was set to RED Added comment: A germline missense variant segregates in one family with autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter (MNG) with schwannomatosis. The missense is also a recurrent somatic missense variant in Wilms tumour. (PMID:31805011) Sources: Literature |
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| Mendeliome v0.2608 | TDRD7 | Zornitza Stark Mode of inheritance for gene: TDRD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2607 | FOXF2 |
Hazel Phillimore gene: FOXF2 was added gene: FOXF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FOXF2 were set to PMID: 30561639; 22022403 Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea Review for gene: FOXF2 was set to AMBER Added comment: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639). This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403). Sources: Literature |
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| Mendeliome v0.2605 | COL13A1 | Zornitza Stark Mode of inheritance for gene: COL13A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2598 | WDR83OS |
Ee Ming Wong gene: WDR83OS was added gene: WDR83OS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WDR83OS were set to PMID: 30250217 Phenotypes for gene: WDR83OS were set to Cholestasis Review for gene: WDR83OS was set to RED Added comment: - 1 consanguineous family with 3 affected individuals found to carry a homozygous splice site variant in WDR83OS - The variant results in an aberrant truncated RNA transcript as demonstrated by RT-PCR Sources: Literature |
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| Mendeliome v0.2592 | LSR |
Ee Ming Wong gene: LSR was added gene: LSR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LSR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSR were set to PMID: 30250217 Phenotypes for gene: LSR were set to transient neonatal cholestasis; intellectual disability; short stature Review for gene: LSR was set to RED Added comment: 1 individual from 1 consanguineous family carrying a homozygous missense variant in LSR Sources: Literature |
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| Mendeliome v0.2591 | USP53 |
Ee Ming Wong gene: USP53 was added gene: USP53 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: USP53 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP53 were set to PMID: 30250217 Phenotypes for gene: USP53 were set to Deafness Review for gene: USP53 was set to RED Added comment: 1 consanguineous family carrying a homozygous truncating variant in USP53 Sources: Literature |
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| Mendeliome v0.2591 | PPM1F |
Ee Ming Wong gene: PPM1F was added gene: PPM1F was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPM1F was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPM1F were set to PMID: 30250217 Phenotypes for gene: PPM1F were set to sclerosing cholangitis; short stature; hypothyroidism; abnormal tongue pigmentation Review for gene: PPM1F was set to RED Added comment: 1 consanguineous family found to carry a homozygous missense variant in PPM1F Sources: Literature |
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| Mendeliome v0.2589 | KLC2 | Zornitza Stark Tag SV/CNV tag was added to gene: KLC2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2588 | KLC2 |
Zornitza Stark gene: KLC2 was added gene: KLC2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KLC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KLC2 were set to 26385635 Phenotypes for gene: KLC2 were set to Spastic paraplegia, optic atrophy, and neuropathy MIM#609541 Review for gene: KLC2 was set to GREEN Added comment: In 73 Brazilian patients and 2 sibs of Egyptian descent with SPOAN, a homozygous 216-bp deletion in the noncoding upstream region of the KLC2 gene was identified. Only reported cause of condition is the upstream large deletion, which is not detected by whole-exome sequencing. Sources: Expert Review |
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| Mendeliome v0.2583 | ALPK1 |
Zornitza Stark gene: ALPK1 was added gene: ALPK1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALPK1 were set to 31053777 Phenotypes for gene: ALPK1 were set to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome Review for gene: ALPK1 was set to AMBER Added comment: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling. Sources: Literature |
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| Mendeliome v0.2581 | LRRC32 |
Zornitza Stark gene: LRRC32 was added gene: LRRC32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC32 were set to 30976112 Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy Review for gene: LRRC32 was set to AMBER Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death. Sources: Literature |
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| Mendeliome v0.2580 | KIF12 |
Ee Ming Wong gene: KIF12 was added gene: KIF12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF12 were set to PMID: 30250217; 30976738 Phenotypes for gene: KIF12 were set to Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT) Review for gene: KIF12 was set to AMBER gene: KIF12 was marked as current diagnostic Added comment: > 3 unrelated families,but they are all consanguineous families Sources: Literature |
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| Mendeliome v0.2574 | IQCE |
Zornitza Stark gene: IQCE was added gene: IQCE was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IQCE were set to 31549751; 28488682 Phenotypes for gene: IQCE were set to Postaxial polydactyly Review for gene: IQCE was set to GREEN Added comment: Four families reported with bi-allelic variants in this gene. The c.895_904del (p.Val301Serfs*8) was found in three of the families without sharing a common haplotype, suggesting a recurrent mechanism. RNA expression analysis on patients’ fibroblasts showed that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrated a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects. Sources: Literature |
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| Mendeliome v0.2573 | NKX2-3 |
Zornitza Stark gene: NKX2-3 was added gene: NKX2-3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NKX2-3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NKX2-3 were set to 31498527 Phenotypes for gene: NKX2-3 were set to Intestinal varicosities Review for gene: NKX2-3 was set to RED Added comment: Single multiplex family where truncating variant in this gene segregated with intestinal varicosities with a LOD score of 3.3. NKX2‐3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice. Sources: Literature |
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| Mendeliome v0.2570 | RPSA | Zornitza Stark Mode of inheritance for gene: RPSA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2566 | CRAT |
Zornitza Stark gene: CRAT was added gene: CRAT was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CRAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CRAT were set to 29395073; 31448845 Phenotypes for gene: CRAT were set to Neurodegeneration with brain iron accumulation 8, MIM# 617917; Leigh syndrome Review for gene: CRAT was set to AMBER Added comment: Two unrelated families reported with bi-allelic variants, one with NBIA and one with Leigh syndrome phenotype. Sources: Literature |
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| Mendeliome v0.2563 | CWF19L1 | Zornitza Stark Mode of inheritance for gene: CWF19L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2559 | B4GAT1 | Zornitza Stark Mode of inheritance for gene: B4GAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2556 | THG1L |
Zornitza Stark changed review comment from: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA. Sources: Literature; to: Four Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA. A carrier rate of 0.8%, but no THG1L V55A homozygotes, was found in a cohort of 3,232 unrelated Ashkenazi Jewish individuals, and no homozygotes found in Exac or gnomAD. Sources: Literature |
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| Mendeliome v0.2554 | THG1L |
Zornitza Stark gene: THG1L was added gene: THG1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: THG1L were set to 27307223; 31168944; 30214071 Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800 Review for gene: THG1L was set to AMBER Added comment: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA. Sources: Literature |
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| Mendeliome v0.2553 | TRPV1 |
Zornitza Stark gene: TRPV1 was added gene: TRPV1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRPV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPV1 were set to 29930394 Phenotypes for gene: TRPV1 were set to Susceptibility to malignant hyperthermia Review for gene: TRPV1 was set to RED Added comment: Two individuals reported with rare/novel missense variants in this gene, some functional data. Sources: Literature |
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| Mendeliome v0.2551 | ZP2 |
Zornitza Stark gene: ZP2 was added gene: ZP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZP2 were set to 30810869; 29895852 Phenotypes for gene: ZP2 were set to Female infertility Review for gene: ZP2 was set to GREEN Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and thin zona pellucida. Sources: Literature |
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| Mendeliome v0.2549 | GAD1 | Zornitza Stark edited their review of gene: GAD1: Added comment: 2020: 11 individuals from 6 consanguineous families reported with bi-allelic LOF variant and a developmental/epileptic encephalopathy. Seizure onset occurred in the first 2 months of life in all. All 10 individuals, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight individuals had joint contractures and/or pes equinovarus. Seven presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1−/− mouse model. Four individuals died before 4 years of age.; Changed rating: GREEN; Changed publications: 15571623, 32282878; Changed phenotypes: Cerebral palsy, spastic quadriplegic, 1, MIM#603513, Developmental and epileptic encephalopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2548 | GALNT2 |
Zornitza Stark gene: GALNT2 was added gene: GALNT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALNT2 were set to 32293671 Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation Review for gene: GALNT2 was set to GREEN Added comment: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. Sources: Literature |
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| Mendeliome v0.2546 | C7orf43 |
Zornitza Stark gene: C7orf43 was added gene: C7orf43 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C7orf43 were set to 30715179 Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351 Review for gene: C7orf43 was set to AMBER Added comment: Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model. Sources: Literature |
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| Mendeliome v0.2541 | GRIN2A | Zornitza Stark Mode of pathogenicity for gene: GRIN2A was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2540 | GRIN2A | Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2538 | TSEN34 | Zornitza Stark Mode of inheritance for gene: TSEN34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2533 | TSEN54 | Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2528 | GABRB2 | Zornitza Stark Mode of pathogenicity for gene: GABRB2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2527 | GABRB2 | Zornitza Stark Mode of inheritance for gene: GABRB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2524 | NDE1 | Zornitza Stark Mode of inheritance for gene: NDE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2521 | CDC45 | Zornitza Stark Mode of inheritance for gene: CDC45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2516 | CHD4 | Zornitza Stark Mode of inheritance for gene: CHD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2513 | RASA1 | Zornitza Stark Mode of inheritance for gene: RASA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2510 | CFAP69 | Zornitza Stark Mode of inheritance for gene: CFAP69 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2507 | ABCA4 | Zornitza Stark Mode of inheritance for gene: ABCA4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2506 | ABCA4 | Zornitza Stark Tag deep intronic tag was added to gene: ABCA4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2504 | TLK2 | Zornitza Stark Mode of inheritance for gene: TLK2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2501 | DYRK1A | Zornitza Stark Mode of inheritance for gene: DYRK1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2494 | SLC35D1 | Zornitza Stark Mode of inheritance for gene: SLC35D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2493 | C1orf194 | Zornitza Stark Mode of pathogenicity for gene: C1orf194 was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2487 | STIM1 | Zornitza Stark Mode of pathogenicity for gene: STIM1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2486 | STIM1 | Zornitza Stark Mode of inheritance for gene: STIM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2483 | ORAI1 | Zornitza Stark Mode of pathogenicity for gene: ORAI1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2482 | ORAI1 | Zornitza Stark Mode of inheritance for gene: ORAI1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2479 | RTTN | Zornitza Stark Mode of inheritance for gene: RTTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2476 | UBAP1 | Zornitza Stark Mode of inheritance for gene: UBAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2470 | ABCC1 |
Zornitza Stark gene: ABCC1 was added gene: ABCC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ABCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ABCC1 were set to 31273342 Phenotypes for gene: ABCC1 were set to Nonsyndromic hearing loss Review for gene: ABCC1 was set to AMBER Added comment: Total of 3 variants reported in 3 families, including 1 which segregates in a large family (10 affected) PMID: 31273342; Li 2019: Reported 3 different het missense in 3 families with postlingual ADNSHL. 1 missense segregated in a large Chinese family. This variant is present in gnomAD (10 hets), but onset noted to be in 2nd or 3rd decade of life. Functional studies performed. Other 2 variants reported absent in gnomAD. Amber rating in light of gnomad frequency of one of the reported variants. Sources: Literature |
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| Mendeliome v0.2467 | GABRA1 | Zornitza Stark Mode of inheritance for gene: GABRA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2464 | SIGMAR1 | Zornitza Stark Mode of inheritance for gene: SIGMAR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2461 | ATOH7 | Zornitza Stark Mode of inheritance for gene: ATOH7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2456 | KLHL24 | Zornitza Stark Mode of inheritance for gene: KLHL24 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2447 | SMCHD1 | Zornitza Stark Mode of inheritance for gene: SMCHD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2444 | CDKL5 | Zornitza Stark Mode of inheritance for gene: CDKL5 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2441 | AEBP1 | Zornitza Stark Mode of inheritance for gene: AEBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | SLC6A6 |
Chern Lim gene: SLC6A6 was added gene: SLC6A6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034 Phenotypes for gene: SLC6A6 were set to Early retinal degeneration; cardiomyopathy Review for gene: SLC6A6 was set to AMBER Added comment: Different homozygous missense variants in 2 unrelated consanguineous families with early retinal degeneration, some functional studies. Patients in one of the families also had cardiomyopathy. (PMIDs: 31345061, 31903486) One dilated cardiomyopathy patient with a homozygous deletion at a splice site (PMID: 29886034). Sources: Literature |
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| Mendeliome v0.2440 | TMPRSS9 |
Chern Lim gene: TMPRSS9 was added gene: TMPRSS9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMPRSS9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMPRSS9 were set to 31943016 Phenotypes for gene: TMPRSS9 were set to autism spectrum disorder Review for gene: TMPRSS9 was set to RED Added comment: Association with Mendelian disease not established. Is a candidate gene for autism spectrum disorder: single patient, compound heterozygous nonsense variants. Functional studies showed Tmprss9 gene is expressed in mouse brain, knockout mice had decreased social interest and social recognition. (PMID: 31943016) Sources: Literature |
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| Mendeliome v0.2440 | MCAT |
Chern Lim gene: MCAT was added gene: MCAT was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MCAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCAT were set to 31915829 Phenotypes for gene: MCAT were set to progressive autosomal recessive optic neuropathy Review for gene: MCAT was set to RED Added comment: One family reported - a consanguineous family, two homozygous missense variants in both affected siblings. Functional studies showed both missense together have synergic impact on MCAT protein misfolding; p.(L81R) had more impact on MCAT protein expression reduction than did the p.(R212W); some study in conditional knockout mice. (PMID:31915829) Sources: Literature |
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| Mendeliome v0.2440 | CAP2 | Melanie Marty edited their review of gene: CAP2: Added comment: 2 patients with dilated cardiomyopathy from 1 consanguineous family. The splice variant identified in this family was proven to cause exon skipping and functional studies showed protein level was reduced. A Cap2 knockout mouse model correlated with the clinical phenotype of DCM and cardiac conduction disease, but not the other effects on growth, viability, wound healing and eye development.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | ATOH7 | Paul De Fazio changed review comment from: Segregates with disease in 3 consanguineous families from Pakistan/Turkey and one non-consanguineous family of Swiss origin. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation.; to: Segregates with disease in 3 consanguineous families from Pakistan/Turkey with global eye abnormalities, and one non-consanguineous family of Swiss origin with optic nerve hypoplasia. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation (in mice). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | UBA2 |
Elena Savva gene: UBA2 was added gene: UBA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: UBA2 were set to PMID: 31332306; 31587267 Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly Penetrance for gene: UBA2 were set to unknown Review for gene: UBA2 was set to AMBER Added comment: No OMIM phenotype PMID: 31332306 - a single patient with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in patients with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC. Sources: Literature |
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| Mendeliome v0.2440 | REC114 |
Michelle Torres gene: REC114 was added gene: REC114 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: REC114 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: REC114 were set to 30388401; 31704776 Phenotypes for gene: REC114 were set to Female infertility Review for gene: REC114 was set to GREEN Added comment: Three variants reported are either within or flanking exon 4. - One hom patient (splice) had a miscarriage, 2 spontaneous complete hydatidiform moles, and 1 complete hydatidiform mole following intrauterine sperm injection (PMID: 30388401) - Two hom unrelated patients from consanguineous families with abnormal pronuclear formation during fertilisation and subsequent early embrionic arrest resulting in female infertility. Both variants (1 missense and 1 splice) were shown to result in LoF (PMID: 31704776) Sources: Literature |
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| Mendeliome v0.2439 | C1orf194 |
Ain Roesley gene: C1orf194 was added gene: C1orf194 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C1orf194 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: C1orf194 were set to PMID: 31199454 Phenotypes for gene: C1orf194 were set to Charcot-Marie-Tooth Review for gene: C1orf194 was set to AMBER Added comment: PMID: 31199454; 2 missense variants in 2 large families segregating in an AD pattern. Mouse models for one of the variants (p.(Ile121Asn) led to impairments in moto and neuromuscular functions Sources: Literature |
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| Mendeliome v0.2439 | POLR1B |
Paul De Fazio gene: POLR1B was added gene: POLR1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR1B were set to 31649276 Phenotypes for gene: POLR1B were set to bilateral malar and mandibular hypoplasia; microtia; coloboma; downslanting palpebral fissures; conductive deafness; cleft palate; heart malformations Review for gene: POLR1B was set to AMBER gene: POLR1B was marked as current diagnostic Added comment: 6 individuals with Treacher-Collins syndrome described: 3 with de novo variants, one inherited from a mosaic father, and two inherited from affected mothers. Knockdown in zebrafish mimics the phenotype. Sources: Literature |
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| Mendeliome v0.2437 | CREB3L1 | Zornitza Stark Mode of inheritance for gene: CREB3L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2436 | WARS |
Naomi Baker gene: WARS was added gene: WARS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783. Phenotypes for gene: WARS were set to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration Review for gene: WARS was set to GREEN Added comment: 14 patients from five families were reported to have WARS-related neuropathy across three publications. Expression studies of mutant demonstrated decreased protein when compared to wild-type. Sources: Literature |
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| Mendeliome v0.2432 | CYLD | Zornitza Stark Mode of inheritance for gene: CYLD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2429 | PCDH19 | Zornitza Stark Mode of inheritance for gene: PCDH19 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2426 | GFAP | Zornitza Stark Mode of inheritance for gene: GFAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2423 | COPA | Zornitza Stark Mode of inheritance for gene: COPA was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2422 | COPA | Zornitza Stark Mode of inheritance for gene: COPA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2421 | PLOD3 | Alison Yeung Mode of inheritance for gene: PLOD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2419 | FOXG1 | Zornitza Stark Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2418 | SAMD12 | Zornitza Stark Tag deep intronic tag was added to gene: SAMD12. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2418 | TBX6 | Alison Yeung Mode of inheritance for gene: TBX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2418 | SAMD12 | Zornitza Stark Mode of inheritance for gene: SAMD12 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2413 | YARS | Zornitza Stark Mode of inheritance for gene: YARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2408 | IGF1R | Zornitza Stark Mode of inheritance for gene: IGF1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2405 | SHANK3 | Zornitza Stark Mode of inheritance for gene: SHANK3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2402 | SCN1A | Zornitza Stark Mode of inheritance for gene: SCN1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2401 | CPSF1 |
Kristin Rigbye changed review comment from: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892). Sources: Literature; to: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (PMID: 30689892). Sources: Literature |
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| Mendeliome v0.2401 | CPSF1 |
Kristin Rigbye gene: CPSF1 was added gene: CPSF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CPSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CPSF1 were set to 30689892 Phenotypes for gene: CPSF1 were set to Myopia 27, 618827; high myopia; early-onset high myopiaHigh myopia Review for gene: CPSF1 was set to GREEN Added comment: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892). Sources: Literature |
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| Mendeliome v0.2399 | STXBP1 | Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2396 | NAA10 | Zornitza Stark Mode of inheritance for gene: NAA10 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2393 | WDR45 | Zornitza Stark Mode of inheritance for gene: WDR45 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2392 | GNAI2 |
Elena Savva gene: GNAI2 was added gene: GNAI2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GNAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GNAI2 were set to PMID: 31036916 Phenotypes for gene: GNAI2 were set to Pituitary adenoma, ACTH-secreting, somatic; Ventricular tachycardia, idiopathic 192605; Syndromic developmental disorder Review for gene: GNAI2 was set to AMBER Added comment: Papers associating this gene to tachycardia are very old (pre 2000, OMIM). PMID: 31036916 - a single de novo patient with syndromic developmental disorder Summary: AMBER - one report, may be a coincidental de novo finding Sources: Literature |
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| Mendeliome v0.2390 | SOD2 | Zornitza Stark Mode of inheritance for gene: SOD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2387 | ASCC1 | Zornitza Stark Mode of inheritance for gene: ASCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2386 | FEM1B |
Elena Savva gene: FEM1B was added gene: FEM1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FEM1B were set to PMID: 31036916 Phenotypes for gene: FEM1B were set to Syndromic global developmental delay Review for gene: FEM1B was set to AMBER Added comment: No OMIM phenotype PMID: 31036916 - a single de novo patient reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. Decipher shows this variant to be in a highly constrained region of the protein. Have selected AMBER for now - not sure if GeneMatcher findings can be used as a 3rd case Sources: Literature |
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| Mendeliome v0.2383 | SMAD2 | Zornitza Stark Mode of inheritance for gene: SMAD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2380 | RXFP2 | Zornitza Stark Mode of inheritance for gene: RXFP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2378 | WIPI2 |
Melanie Marty gene: WIPI2 was added gene: WIPI2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WIPI2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WIPI2 were set to 30968111 Phenotypes for gene: WIPI2 were set to Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 Review for gene: WIPI2 was set to AMBER Added comment: Four homozygous patients from one consanguineous family with intellectual developmental, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function. Sources: Literature |
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| Mendeliome v0.2378 | SEC31A |
Hazel Phillimore gene: SEC31A was added gene: SEC31A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEC31A were set to PMID: 30464055 Phenotypes for gene: SEC31A were set to congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive Review for gene: SEC31A was set to AMBER Added comment: Frameshift. c.2776_2777, TA duplication, causing predicted p.A927fs*61 truncation and predicted NMD in 2 affected siblings in consanguineous Bedouin family with severe congenital neurological syndrome with spastic paraplegia, multiple contractures, profound developmental delay and convulsions. Failure to thrive. Lethal by age 4 years. Also had hearing defect, bilateral congenital cataract, horizontal nystagmus, with flat retina and optic atrophy. Supporting functional assays from knockout drosophila. Sources: Literature |
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| Mendeliome v0.2378 | SLC44A1 |
Sebastian Lunke gene: SLC44A1 was added gene: SLC44A1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC44A1 were set to 31855247 Phenotypes for gene: SLC44A1 were set to progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria Review for gene: SLC44A1 was set to GREEN Added comment: Four affected individuals from three families with homozygous frameshift variants. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial. Sources: Literature |
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| Mendeliome v0.2377 | GSX2 |
Elena Savva gene: GSX2 was added gene: GSX2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GSX2 were set to PMID: 31412107 Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646 Review for gene: GSX2 was set to GREEN Added comment: PMID: 31412107 - 2 unrelated patients with homozygous mutations (nonsense, missense). Functional analysis of the missense in transfected HeLa cells demonstrated protein mislocalization and protein expression. Downstream gene expression was also reduced by both mutations. Summary: GREEN - 2 patients and functional evidence Sources: Literature |
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| Mendeliome v0.2375 | SPEF2 |
Chern Lim gene: SPEF2 was added gene: SPEF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPEF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPEF2 were set to 31151990; 31278745; 31048344 Phenotypes for gene: SPEF2 were set to Spermatogenic failure 43, MIM#618751 Review for gene: SPEF2 was set to GREEN gene: SPEF2 was marked as current diagnostic Added comment: More than 3 unrelated families reported, all PTVs or splice variant. Functional studies showed SPEF2 protein levels were reduced in patients’ spermatozoa. (PMIDs: 31151990, 31278745, 31048344). Sources: Literature |
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| Mendeliome v0.2373 | DHH | Zornitza Stark Mode of inheritance for gene: DHH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2372 | ACKR3 |
Elena Savva gene: ACKR3 was added gene: ACKR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ACKR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACKR3 were set to PMID: 3121183 Phenotypes for gene: ACKR3 were set to Oculomotor synkinesis Review for gene: ACKR3 was set to AMBER Added comment: No phenotype currently listed in OMIM PMID: 3121183 - 1 family (3 siblings and a cousin) with congenital ptosis and oculomotor synkinesis. Mouse model reciprocated the phenotype. Functional assay using transfected HEK293 cells show protein mislocalization and lower binding affinity Emerging gene-disease association Sources: Literature |
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| Mendeliome v0.2369 | MYCN | Zornitza Stark Mode of inheritance for gene: MYCN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2367 | CNNM4 | Zornitza Stark Mode of inheritance for gene: CNNM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2366 | ATM | Zornitza Stark Mode of inheritance for gene: ATM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2365 | SAMD12 |
Melanie Marty gene: SAMD12 was added gene: SAMD12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SAMD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SAMD12 were set to 30194086; 29507423 Phenotypes for gene: SAMD12 were set to Epilepsy, familial adult myoclonic, 1 601068 Review for gene: SAMD12 was set to GREEN Added comment: Repeat expansions of intronic TTTCA and TTTTA motifs within SAMD12 have been identified in over 50 Japanese and Chinese families. Most families with affected individuals were heterozygous however 4 patients from 3 families had homozygous repeat expansions, which was associated with a more severe phenotype. Western blot analysis showed decreased levels of the protein in patient brains. Sources: Literature |
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| Mendeliome v0.2365 | FUS |
Elena Savva gene: FUS was added gene: FUS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FUS were set to PMID: 32281455; 20668259; 20385912 Phenotypes for gene: FUS were set to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia 608030; Essential tremor, hereditary, 4 614782 Mode of pathogenicity for gene: FUS was set to Other Review for gene: FUS was set to GREEN Added comment: PMID: 32281455 - Reports a case of Pediatric Amyotrophic Lateral Sclerosis. Reviews and shows multiple other reports of ALS casued by FUS PMID: 20668259 - additional reports of ALS PMID: 20385912 - postulated that disruption of this region may disrupt subcellular distribution of FUS, in turn affecting transcription and RNA processing and conferring a toxic gain of function. Sources: Literature |
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| Mendeliome v0.2365 | ADAMTS19 |
Crystle Lee gene: ADAMTS19 was added gene: ADAMTS19 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ADAMTS19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS19 were set to 31844321 Phenotypes for gene: ADAMTS19 were set to Non-syndromic heart valve disease Review for gene: ADAMTS19 was set to GREEN Added comment: PMID: 31844321; Wünnemann 2020: 4 affected in unrelated 2 consanguineous family with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review |
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| Mendeliome v0.2365 | C9orf72 |
Elena Savva gene: C9orf72 was added gene: C9orf72 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: C9orf72 were set to PMID: 30120348; 23284068 Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 Review for gene: C9orf72 was set to AMBER Added comment: Possibly RED Caused by expansion of GGGGCC repeats, dont know if these qualify for mendeliome Sources: Literature |
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| Mendeliome v0.2364 | CFAP65 |
Daniel Flanagan gene: CFAP65 was added gene: CFAP65 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP65 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP65 were set to 31501240; 31413122 Phenotypes for gene: CFAP65 were set to Spermatogenic failure 40 618664 Penetrance for gene: CFAP65 were set to unknown Review for gene: CFAP65 was set to GREEN gene: CFAP65 was marked as current diagnostic Added comment: 9 patients with multiple morphological abnormalities of the sperm flagella (MMAF) or completely immotile spermatozoa, in which, homozygous or compound heterozygous truncating CFAP65 variants were identified. Cfap65-mutated male mice displayed typical MMAF phenotypes with severe morphological abnormalities of the sperm flagella (PMID: 31501240, 31413122). Sources: Literature |
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| Mendeliome v0.2364 | CAP2 |
Melanie Marty gene: CAP2 was added gene: CAP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAP2 were set to 30518548 Phenotypes for gene: CAP2 were set to Dilated cardiomyopathy Review for gene: CAP2 was set to AMBER Added comment: 2 patients with dilated cardiomyopathy from 1 consanguineous family. The splice variant identified in this family was proven to cause exon skipping and functional studies showed protein level was reduced. A Cap2 knockout mouse model correlated with the clinical phenotype of DCM and cardiac conduction disease, but not the other effects on growth, viability, wound healing and eye development. Sources: Literature |
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| Mendeliome v0.2362 | SYCP2 |
Zornitza Stark gene: SYCP2 was added gene: SYCP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SYCP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SYCP2 were set to 32092049; 31866047 Phenotypes for gene: SYCP2 were set to Male infertility Review for gene: SYCP2 was set to GREEN Added comment: Four individuals and a zebrafish model. Sources: Literature |
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| Mendeliome v0.2361 | PKDCC |
Paul De Fazio gene: PKDCC was added gene: PKDCC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PKDCC were set to PMID:30478137; 19097194 Phenotypes for gene: PKDCC were set to Dysmorphism; shortening of extremities Review for gene: PKDCC was set to AMBER gene: PKDCC was marked as current diagnostic Added comment: 2 ("apparently") unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice. Sources: Literature |
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| Mendeliome v0.2361 | TNFRSF21 |
Shannon Cowie gene: TNFRSF21 was added gene: TNFRSF21 was added to Mendeliome. Sources: Other Mode of inheritance for gene: TNFRSF21 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TNFRSF21 were set to PMID: 31189563 Phenotypes for gene: TNFRSF21 were set to high myopia Review for gene: TNFRSF21 was set to RED gene: TNFRSF21 was marked as current diagnostic Added comment: Source: JMG review Oct 2019 Large Chinese family, including 12 patients with non-syndromic HM Immunofluorescence assay indicated that it is strongly expressed in the mouse eye. Sources: Other |
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| Mendeliome v0.2361 | USP45 |
Kristin Rigbye gene: USP45 was added gene: USP45 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: USP45 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP45 were set to 30573563 Phenotypes for gene: USP45 were set to Leber congenital amaurosis; retinal dystrophy Review for gene: USP45 was set to GREEN Added comment: 2 unrelated Chinese families reported with rare homozygous variants (one missense, one nonsense) and Leber congenital amaurosis. Animal knockout functional studies supported gene-disease association. PMID: 30573563 "By analysing WES data based on allele frequencies of in-house controls, population allele frequencies and in silico prediction tools, two rare homozygous mutations in USP45 were identified in two unrelated families. Immunohistochemistry of USP45 in the human and zebrafish retinal sections revealed enriched expression in the inner segments of photoreceptors. The knockdown of usp45 transcript in zebrafish led to abnormal retinal development with effects on photoreceptors, which could be successfully rescued by wild-type usp45 mRNA. Moreover, targeted knockout of Usp45 in mice caused abnormal electroretinography responses, similar to that seen in patients with LCA." Sources: Literature |
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| Mendeliome v0.2360 | BAZ2B |
Zornitza Stark gene: BAZ2B was added gene: BAZ2B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BAZ2B were set to 31999386; 28135719; 25363768 Phenotypes for gene: BAZ2B were set to Intellectual disability; autism Review for gene: BAZ2B was set to GREEN Added comment: Postulated as a candidate gene for ID/ASD by large-scale studies. Case series reports two individuals with small CNVs and and six with SNVs, mostly LoF type variants. Although the gene is generally intolerant of LoF, some LoF variants present in gnomad ?incomplete penetrance. Additional reported features were inconsistent Sources: Literature |
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| Mendeliome v0.2358 | TPI1 |
Zornitza Stark gene: TPI1 was added gene: TPI1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TPI1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TPI1 were set to Hemolytic anemia due to triosephosphate isomerase deficiency, MIM# 615512 Review for gene: TPI1 was set to GREEN Added comment: Sources: Expert list |
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| Mendeliome v0.2356 | EMG1 |
Zornitza Stark gene: EMG1 was added gene: EMG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: EMG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EMG1 were set to 19463982 Phenotypes for gene: EMG1 were set to Bowen-Conradi syndrome, MIM#211180 Review for gene: EMG1 was set to AMBER Added comment: Founder mutation in Hutterite, D86G. Sources: Expert list |
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| Mendeliome v0.2354 | EIF2AK4 |
Zornitza Stark gene: EIF2AK4 was added gene: EIF2AK4 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: EIF2AK4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EIF2AK4 were set to Pulmonary venoocclusive disease 2, MIM#234810 Review for gene: EIF2AK4 was set to GREEN Added comment: Sources: Expert list |
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| Mendeliome v0.2352 | AGBL5 |
Zornitza Stark gene: AGBL5 was added gene: AGBL5 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AGBL5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGBL5 were set to 26720455; 26355662; 30925032 Phenotypes for gene: AGBL5 were set to Retinitis pigmentosa 75, MIM# 617023 Review for gene: AGBL5 was set to GREEN Added comment: At least three unrelated families reported. Sources: Expert list |
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| Mendeliome v0.2350 | CPT1C |
Bryony Thompson gene: CPT1C was added gene: CPT1C was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CPT1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CPT1C were set to 25751282; 23973755 Phenotypes for gene: CPT1C were set to Spastic paraplegia 73, autosomal dominant MIM#616282 Review for gene: CPT1C was set to GREEN Added comment: Two unrelated families dominant HSP and a supportive mouse model. Sources: Expert list |
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| Mendeliome v0.2348 | ATP2B4 |
Bryony Thompson gene: ATP2B4 was added gene: ATP2B4 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ATP2B4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP2B4 were set to 25119969; 25798335; 29691679 Phenotypes for gene: ATP2B4 were set to Hereditary spastic paraplegia Review for gene: ATP2B4 was set to AMBER Added comment: One Chinese family segregating a missense variant with HSP and one HSP case with a assumed de novo nonsense variant. Supporting in vitro functional assays for the missense variant. Sources: Expert list |
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| Mendeliome v0.2343 | SEC63 | Zornitza Stark Mode of inheritance for gene: SEC63 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2340 | CYP1B1 | Zornitza Stark Mode of inheritance for gene: CYP1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2337 | DAG1 | Zornitza Stark Mode of inheritance for gene: DAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2334 | DPYD | Zornitza Stark Mode of inheritance for gene: DPYD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2331 | MFSD8 | Zornitza Stark Mode of inheritance for gene: MFSD8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2329 | NF1 | Zornitza Stark Mode of inheritance for gene: NF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2326 | TECTA | Zornitza Stark Mode of pathogenicity for gene: TECTA was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2325 | TECTA | Zornitza Stark Mode of inheritance for gene: TECTA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2321 | TRAPPC9 | Zornitza Stark Mode of inheritance for gene: TRAPPC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2318 | SOS1 | Zornitza Stark Mode of pathogenicity for gene: SOS1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2317 | SOS1 | Zornitza Stark Mode of inheritance for gene: SOS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2314 | F11 | Zornitza Stark Mode of inheritance for gene: F11 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2312 | FMR1 | Bryony Thompson Tag STR tag was added to gene: FMR1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2312 | DMPK | Bryony Thompson Tag STR tag was added to gene: DMPK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2311 | MED13L | Zornitza Stark Mode of inheritance for gene: MED13L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2310 | BEAN1 | Bryony Thompson Tag STR tag was added to gene: BEAN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2307 | PROKR2 | Zornitza Stark Mode of pathogenicity for gene: PROKR2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2306 | PROKR2 | Zornitza Stark Mode of inheritance for gene: PROKR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2304 | XRCC1 |
Bryony Thompson gene: XRCC1 was added gene: XRCC1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: XRCC1 were set to 28002403; 29472272 Phenotypes for gene: XRCC1 were set to Spinocerebellar ataxia, autosomal recessive 26 MIM#617633 Review for gene: XRCC1 was set to GREEN Added comment: Three South Asian cases (one with early adult onset and the other two with onset in childhood) reported with slowly progressive cerebellar ataxia accompanied by sensorimotor neuropathy. All with the recurrent splice variant (c.1293G>C, 2 homozygotes and a compound heterozygote). Mice with conditional deletion of the Xrcc1 gene in the brain showed cerebellar ataxia. Sources: Expert list |
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| Mendeliome v0.2302 | TRPC3 |
Bryony Thompson gene: TRPC3 was added gene: TRPC3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPC3 were set to 25477146; 19351902 Phenotypes for gene: TRPC3 were set to Spinocerebellar ataxia 41 MIM#616410 Mode of pathogenicity for gene: TRPC3 was set to Other Review for gene: TRPC3 was set to AMBER Added comment: A heterozygous gain-of function missense has been identified in a 40-year-old man with adult-onset spinocerebellar ataxia. A mouse model of dominant cerebellar ataxia, termed 'moonwalker', contains a gain-of-function variant in this gene. Sources: Expert list |
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| Mendeliome v0.2300 | SLC9A1 |
Zornitza Stark gene: SLC9A1 was added gene: SLC9A1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC9A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC9A1 were set to 25205112; 30018422; 25760855 Phenotypes for gene: SLC9A1 were set to Lichtenstein-Knorr syndrome, MIM# 616291 Review for gene: SLC9A1 was set to AMBER Added comment: Two families with bi-allelic variants in this gene reported and combination of deafness and ataxia. Sources: Expert list |
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| Mendeliome v0.2298 | MTCL1 |
Bryony Thompson gene: MTCL1 was added gene: MTCL1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MTCL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MTCL1 were set to 30548255; 28283581 Phenotypes for gene: MTCL1 were set to slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia Review for gene: MTCL1 was set to AMBER Added comment: Single case with a homozygous loss of function variant in a Polish study of early-onset cerebellar ataxia, and a single family with a single heterozygous missense (p.Val1435Met) identified in two family members with adult-onset spinocerebellar ataxia. Mtcl1 gene disruption in mice results in abnormal motor coordination with Purkinje cell degeneration Sources: Expert list |
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| Mendeliome v0.2296 | ATG5 |
Bryony Thompson gene: ATG5 was added gene: ATG5 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ATG5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATG5 were set to 16625204; 26812546 Phenotypes for gene: ATG5 were set to Spinocerebellar ataxia, autosomal recessive 25 MIM#617584 Review for gene: ATG5 was set to AMBER Added comment: A homozgyous variant was identified in a single family with two affected siblings. Mice deficient for Atg5 specifically in neural cells and Atg5 null Drosophila develop progressive deficits in motor function. Sources: Expert list |
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| Mendeliome v0.2295 | IL18BP |
Zornitza Stark gene: IL18BP was added gene: IL18BP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL18BP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL18BP were set to 31213488 Phenotypes for gene: IL18BP were set to {?Hepatitis, fulminant viral, susceptibility to} 618549 Review for gene: IL18BP was set to RED Added comment: Single individual reported with homozygous 40bp deletion in this gene and fulminant Hep A hepatitis. Sources: Expert list |
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| Mendeliome v0.2292 | IRF4 | Zornitza Stark Mode of inheritance for gene: IRF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2289 | ACOX2 |
Zornitza Stark gene: ACOX2 was added gene: ACOX2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACOX2 were set to 27647924; 27884763 Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6, 617308 Review for gene: ACOX2 was set to AMBER Added comment: Two unrelated families reported. Sources: Expert Review |
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| Mendeliome v0.2287 | LARS |
Zornitza Stark gene: LARS was added gene: LARS was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LARS were set to 28774368; 30349989; 22607940 Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438 Review for gene: LARS was set to GREEN gene: LARS was marked as current diagnostic Added comment: Six unrelated families reported in the literature, reviewed in PMID: 30349989. Sources: NHS GMS |
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| Mendeliome v0.2284 | KCNJ11 | Zornitza Stark Mode of pathogenicity for gene: KCNJ11 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2283 | KCNJ11 | Zornitza Stark Mode of inheritance for gene: KCNJ11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2281 | SIPA1L3 |
Bryony Thompson gene: SIPA1L3 was added gene: SIPA1L3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SIPA1L3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SIPA1L3 were set to 28951961; 27993984; 25804400 Phenotypes for gene: SIPA1L3 were set to Cataract 45 MIM#616851 Review for gene: SIPA1L3 was set to AMBER Added comment: A consanguineous German family segregating a homozygous nonsense mutation in two sisters with congenital cataracts (PMID: 25804400). Null Zebrafish, Xenopus and mouse models recapitulate the human cataract phenotype. A case with congenital cataracts as a feature of their condition harboured a de novo balanced chromosomal translocation, 46,XY,t(2;19)(q37.3;q13.1), where breakpoint mapping and sequencing showed a physical disruption of the 5′UTR of SIPA1L3 (PMID: 26231217). In a case with bilateral congenital cataracts a heterozygous missense (D148Y) was identified and in vitro functional assays of the variant resulted in abnormal actin morphology (PMID: 26231217). Sources: Expert list |
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| Mendeliome v0.2279 | SLC18A2 |
Zornitza Stark gene: SLC18A2 was added gene: SLC18A2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC18A2 were set to 23363473; 31240161; 26497564 Phenotypes for gene: SLC18A2 were set to Parkinsonism-dystonia, infantile, 2, MIM# 618049 Review for gene: SLC18A2 was set to GREEN Added comment: At least three unrelated families reported, potential treatment implications Sources: Expert Review |
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| Mendeliome v0.2276 | RNU4ATAC | Zornitza Stark Mode of inheritance for gene: RNU4ATAC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2273 | IFT172 | Zornitza Stark Mode of inheritance for gene: IFT172 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2270 | KMT2E | Zornitza Stark Mode of inheritance for gene: KMT2E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2267 | MAP1B | Zornitza Stark Mode of inheritance for gene: MAP1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2264 | MAP3K7 | Zornitza Stark Mode of pathogenicity for gene: MAP3K7 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2263 | MAP3K7 | Zornitza Stark Mode of inheritance for gene: MAP3K7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2260 | MARS2 | Zornitza Stark Mode of inheritance for gene: MARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2257 | MECOM | Zornitza Stark Mode of inheritance for gene: MECOM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2254 | MED17 | Zornitza Stark Mode of inheritance for gene: MED17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2251 | NEBL | Zornitza Stark Mode of inheritance for gene: NEBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2249 | NPHP3 | Zornitza Stark Mode of inheritance for gene: NPHP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2243 | PAX1 | Zornitza Stark Mode of inheritance for gene: PAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2240 | PDE8B | Zornitza Stark Mode of inheritance for gene: PDE8B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2235 | PIGG | Zornitza Stark Mode of inheritance for gene: PIGG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2232 | PIGU | Zornitza Stark Mode of inheritance for gene: PIGU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2229 | PUS3 | Zornitza Stark Mode of inheritance for gene: PUS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2226 | RUBCN | Zornitza Stark Mode of inheritance for gene: RUBCN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2223 | SHANK2 | Zornitza Stark Mode of inheritance for gene: SHANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2220 | SLC26A4 | Zornitza Stark Mode of inheritance for gene: SLC26A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2217 | SMPD4 | Zornitza Stark Mode of inheritance for gene: SMPD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2214 | SOX11 | Zornitza Stark Mode of inheritance for gene: SOX11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2209 | QRSL1 | Zornitza Stark Mode of inheritance for gene: QRSL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2206 | PPCS | Zornitza Stark Mode of inheritance for gene: PPCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2204 | PET117 |
Zornitza Stark gene: PET117 was added gene: PET117 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PET117 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PET117 were set to 28386624 Phenotypes for gene: PET117 were set to Developmental delay; Regression; Complex IV deficiency Review for gene: PET117 was set to RED Added comment: Two siblings reported, some functional data. PET117 postulated to be a Complex IV assembly factor. Sources: Expert list |
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| Mendeliome v0.2196 | TBCD | Zornitza Stark Mode of inheritance for gene: TBCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2195 | TMTC2 | Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2186 | WNT10A | Zornitza Stark Mode of inheritance for gene: WNT10A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2184 | ZNF592 | Zornitza Stark Mode of inheritance for gene: ZNF592 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2179 | NME3 |
Zornitza Stark gene: NME3 was added gene: NME3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NME3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NME3 were set to 30587587 Phenotypes for gene: NME3 were set to Hypotonia; Neurodegeneration; Abnormal mitochondrial dynamics Review for gene: NME3 was set to RED Added comment: Single individual reported. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics Sources: Expert list |
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| Mendeliome v0.2178 | MRPS28 |
Zornitza Stark gene: MRPS28 was added gene: MRPS28 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MRPS28 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS28 were set to 30566640 Phenotypes for gene: MRPS28 were set to Intrauterine growth retardation; developmental delay; dysmorphism Review for gene: MRPS28 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.2177 | MRPS25 |
Zornitza Stark gene: MRPS25 was added gene: MRPS25 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MRPS25 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS25 were set to 31039582 Phenotypes for gene: MRPS25 were set to Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum Review for gene: MRPS25 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.2173 | MIEF2 |
Zornitza Stark gene: MIEF2 was added gene: MIEF2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MIEF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIEF2 were set to 29361167 Phenotypes for gene: MIEF2 were set to Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency Review for gene: MIEF2 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.2171 | ERAL1 |
Zornitza Stark gene: ERAL1 was added gene: ERAL1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERAL1 were set to 28449065 Phenotypes for gene: ERAL1 were set to Perrault syndrome 6, MIM# 617565 Review for gene: ERAL1 was set to AMBER Added comment: Three individuals from same small geographical location with homozygous missense variant in this gene, functional data. Sources: Expert list |
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| Mendeliome v0.2170 | COX5A |
Zornitza Stark gene: COX5A was added gene: COX5A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: COX5A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX5A were set to 2824752 Phenotypes for gene: COX5A were set to pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency Review for gene: COX5A was set to RED Added comment: Single family reported. Sources: Expert list |
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| Mendeliome v0.2167 | TRAF3IP2 | Zornitza Stark Mode of inheritance for gene: TRAF3IP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2163 | TRAF3 | Zornitza Stark Mode of inheritance for gene: TRAF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2159 | TNFSF12 | Zornitza Stark Mode of inheritance for gene: TNFSF12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2155 | TNFRSF4 | Zornitza Stark Mode of inheritance for gene: TNFRSF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2151 | TNFRSF13C | Zornitza Stark Mode of inheritance for gene: TNFRSF13C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2147 | TNFRSF13B | Zornitza Stark Mode of inheritance for gene: TNFRSF13B was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2144 | THBD | Zornitza Stark Mode of inheritance for gene: THBD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2141 | TAPBP | Zornitza Stark Mode of inheritance for gene: TAPBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2138 | NXN | Zornitza Stark Mode of inheritance for gene: NXN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2133 | SEMA3E | Zornitza Stark Mode of inheritance for gene: SEMA3E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2130 | RNF31 | Zornitza Stark Mode of inheritance for gene: RNF31 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2126 | RHOH | Zornitza Stark Mode of inheritance for gene: RHOH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2122 | PSMB9 | Zornitza Stark Mode of inheritance for gene: PSMB9 was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2118 | PSMB4 | Zornitza Stark Mode of inheritance for gene: PSMB4 was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2114 | PSMA3 | Zornitza Stark Mode of inheritance for gene: PSMA3 was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2108 | NFAT5 | Zornitza Stark Mode of inheritance for gene: NFAT5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2104 | MS4A1 | Zornitza Stark Mode of inheritance for gene: MS4A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2101 | MASP2 | Zornitza Stark Mode of inheritance for gene: MASP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2096 | IRF7 | Zornitza Stark Mode of inheritance for gene: IRF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2092 | IL21 | Zornitza Stark Mode of inheritance for gene: IL21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2088 | IL17F | Zornitza Stark Mode of inheritance for gene: IL17F was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2081 | FCN3 | Zornitza Stark Mode of inheritance for gene: FCN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2077 | FCGR3A | Zornitza Stark Mode of inheritance for gene: FCGR3A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2073 | CR2 | Zornitza Stark Mode of inheritance for gene: CR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2068 | CFHR2 | Zornitza Stark Mode of inheritance for gene: CFHR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2067 | CFHR2 | Zornitza Stark Tag SV/CNV tag was added to gene: CFHR2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2065 | CFB | Zornitza Stark Mode of inheritance for gene: CFB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2061 | CFB | Zornitza Stark Mode of inheritance for gene: CFB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2057 | CD8A | Zornitza Stark Mode of inheritance for gene: CD8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2053 | CD81 | Zornitza Stark Mode of inheritance for gene: CD81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2050 | CD247 | Zornitza Stark changed review comment from: Also known as CD3Z. Single individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants.; to: Also known as CD3Z. Note one individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2047 | BLOC1S6 | Zornitza Stark Mode of inheritance for gene: BLOC1S6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2044 | MIR140 |
Zornitza Stark gene: MIR140 was added gene: MIR140 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: MIR140 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MIR140 were set to 30804514; 31633310 Phenotypes for gene: MIR140 were set to Spondyloepiphyseal dysplasia, Nishimura type, MIM# 618618 Review for gene: MIR140 was set to GREEN Added comment: Single clinical paper (30804514) reports variant in affected mother and child (de novo in mother) and in a separate unrelated female (de novo) with spondylo-epiphyseal dysplasia. Mouse model (21576357) deletion of gene causes impaired longitudinal bone growth. Separate mouse model studies by same authors as clinical paper above (30804514) showed phenotype of mice with same mutation in this gene consistent with the skeletal dysplasia features of patients with the n.24A-G mutation, suggestive of neomorphic effects (mutation produces both loss-of-function and gain-of-function effects.) Sources: Expert Review |
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| Mendeliome v0.2043 | APOL1 | Zornitza Stark Mode of inheritance for gene: APOL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2037 | AP1S3 | Zornitza Stark Mode of inheritance for gene: AP1S3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2031 | PIEZO1 | Zornitza Stark Mode of pathogenicity for gene: PIEZO1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2030 | PIEZO1 | Zornitza Stark Mode of inheritance for gene: PIEZO1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2027 | TBX19 | Zornitza Stark Mode of inheritance for gene: TBX19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2024 | TCF20 | Zornitza Stark Mode of inheritance for gene: TCF20 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2021 | TFE3 | Zornitza Stark Mode of inheritance for gene: TFE3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2018 | ICOSLG | Zornitza Stark Mode of inheritance for gene: ICOSLG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2014 | IL6ST | Zornitza Stark Mode of inheritance for gene: IL6ST was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2011 | SAMD9L | Zornitza Stark Mode of pathogenicity for gene: SAMD9L was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2010 | SAMD9L | Zornitza Stark Mode of inheritance for gene: SAMD9L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2007 | RFWD3 | Zornitza Stark Mode of inheritance for gene: RFWD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2005 | MAD2L2 |
Zornitza Stark gene: MAD2L2 was added gene: MAD2L2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MAD2L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAD2L2 were set to 27500492 Phenotypes for gene: MAD2L2 were set to Fanconi anemia, complementation group V, MIM# 617243 Review for gene: MAD2L2 was set to RED Added comment: Single family reported. Sources: Expert list |
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| Mendeliome v0.2002 | UBE2T | Zornitza Stark Mode of inheritance for gene: UBE2T was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1999 | HAVCR2 |
Zornitza Stark gene: HAVCR2 was added gene: HAVCR2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HAVCR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HAVCR2 were set to 30374066; 30792187 Phenotypes for gene: HAVCR2 were set to T-cell lymphoma, subcutaneous panniculitis-like, MIM# 618398 Review for gene: HAVCR2 was set to GREEN Added comment: Over 20 unrelated individuals reported, note germline confirmation in only a few. Some variants are recurrent: c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met). Sources: Expert list |
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| Mendeliome v0.1997 | TRIM22 |
Zornitza Stark gene: TRIM22 was added gene: TRIM22 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRIM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRIM22 were set to 26836588 Phenotypes for gene: TRIM22 were set to Inflammatory bowel disease Review for gene: TRIM22 was set to GREEN Added comment: Three unrelated families reported with bi-allelic variants in this gene, and very early onset IBD, some functional data. Sources: Expert list |
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| Mendeliome v0.1995 | ALPI |
Zornitza Stark gene: ALPI was added gene: ALPI was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ALPI was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALPI were set to 29567797 Phenotypes for gene: ALPI were set to Inflammatory bowel disease Review for gene: ALPI was set to AMBER Added comment: Two unrelated individuals, some functional data. Sources: Expert list |
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| Mendeliome v0.1994 | PSMG2 |
Zornitza Stark gene: PSMG2 was added gene: PSMG2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PSMG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMG2 were set to 30664889 Phenotypes for gene: PSMG2 were set to CANDLE syndrome; Chronic atypical neutrophilic dermatitis with lipodystrophy Review for gene: PSMG2 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.1991 | NLRP1 | Zornitza Stark Mode of inheritance for gene: NLRP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1988 | POLA1 | Zornitza Stark Mode of inheritance for gene: POLA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1987 | POLA1 | Zornitza Stark Tag deep intronic tag was added to gene: POLA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1987 | IRAK1 | Zornitza Stark Tag SV/CNV tag was added to gene: IRAK1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1987 | IRAK1 |
Zornitza Stark gene: IRAK1 was added gene: IRAK1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IRAK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: IRAK1 were set to 28069966 Phenotypes for gene: IRAK1 were set to Susceptibility to bacterial infections Review for gene: IRAK1 was set to RED Added comment: Single individual with MECP2 and IRAK1 deletion, died in infancy, immunological phenotype not fully elucidated. In vitro studies. Sources: Expert list |
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| Mendeliome v0.1985 | DBR1 |
Zornitza Stark gene: DBR1 was added gene: DBR1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DBR1 were set to 29474921 Phenotypes for gene: DBR1 were set to Viral infections of the brainstem Review for gene: DBR1 was set to GREEN Added comment: Seven individuals from three unrelated families with viral brainstem encephalitis and bi-allelic hypomorphic variants. Sources: Expert list |
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| Mendeliome v0.1984 | POLR3F |
Zornitza Stark gene: POLR3F was added gene: POLR3F was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: POLR3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR3F were set to 30211253 Phenotypes for gene: POLR3F were set to Severe VZV infection Review for gene: POLR3F was set to RED Added comment: Missense variant identified in a pair of monozygotic twins. Variant was paternally inherited. Sources: Expert list |
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| Mendeliome v0.1982 | POLR3C |
Zornitza Stark gene: POLR3C was added gene: POLR3C was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: POLR3C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR3C were set to 28783042 Phenotypes for gene: POLR3C were set to Severe VZV infection Review for gene: POLR3C was set to AMBER Added comment: One individual with POLR3C variant and another individual with both POL3RA and POL3RC variants. Sources: Expert list |
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| Mendeliome v0.1980 | POLR3A | Zornitza Stark Mode of inheritance for gene: POLR3A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1977 | IFNAR2 | Zornitza Stark Mode of inheritance for gene: IFNAR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1974 | IFNAR1 |
Zornitza Stark gene: IFNAR1 was added gene: IFNAR1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IFNAR1 were set to 31270247 Phenotypes for gene: IFNAR1 were set to Severe disease caused by Yellow Fever vaccine and Measles vaccine Review for gene: IFNAR1 was set to AMBER Added comment: Two unrelated individuals reported with bi-allelic LoF variants, some functional data. Sources: Expert list |
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| Mendeliome v0.1972 | IRF9 |
Zornitza Stark gene: IRF9 was added gene: IRF9 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IRF9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IRF9 were set to 30826365; 30143481 Phenotypes for gene: IRF9 were set to Immunodeficiency 65, susceptibility to viral infections 618648 Review for gene: IRF9 was set to AMBER Added comment: Two families reported. Sources: Expert list |
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| Mendeliome v0.1970 | CIB1 |
Zornitza Stark gene: CIB1 was added gene: CIB1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CIB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CIB1 were set to 30068544 Phenotypes for gene: CIB1 were set to Epidermodysplasia verruciformis 3 618267; HPV infections and cancer of the skin Review for gene: CIB1 was set to GREEN Added comment: 24 individuals from 6 families reported. Sources: Expert list |
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| Mendeliome v0.1967 | JAK1 | Zornitza Stark Mode of inheritance for gene: JAK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1964 | SPPL2A |
Zornitza Stark gene: SPPL2A was added gene: SPPL2A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SPPL2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPPL2A were set to 30127434 Phenotypes for gene: SPPL2A were set to Susceptibility to mycobacteria and Salmonella Review for gene: SPPL2A was set to AMBER Added comment: Three individuals from two unrelated consanguineous family with two different homozygous splice site variants, functional data. Sources: Expert list |
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| Mendeliome v0.1961 | IL23R | Zornitza Stark Mode of inheritance for gene: IL23R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1959 | IL12RB2 |
Zornitza Stark gene: IL12RB2 was added gene: IL12RB2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL12RB2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL12RB2 were set to 30578351 Phenotypes for gene: IL12RB2 were set to Susceptibility to mycobacteria and Salmonella Review for gene: IL12RB2 was set to RED Added comment: Single individual reported, some functional data. Sources: Expert list |
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| Mendeliome v0.1957 | C17orf62 |
Zornitza Stark gene: C17orf62 was added gene: C17orf62 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C17orf62 were set to 30361506; 30312704; 28351984 Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease Review for gene: C17orf62 was set to GREEN Added comment: Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name) Sources: Expert list |
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| Mendeliome v0.1955 | MKL1 |
Zornitza Stark gene: MKL1 was added gene: MKL1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MKL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MKL1 were set to 32128589; 26224645 Phenotypes for gene: MKL1 were set to Neutropaenia with combined immune deficiency Review for gene: MKL1 was set to AMBER Added comment: Two unrelated families reported. Sources: Expert list |
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| Mendeliome v0.1954 | HYOU1 |
Zornitza Stark gene: HYOU1 was added gene: HYOU1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HYOU1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HYOU1 were set to 27913302 Phenotypes for gene: HYOU1 were set to Immunodeficiency 59 and hypoglycemia, MIM# 233600 Review for gene: HYOU1 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.1952 | SMARCD2 |
Zornitza Stark gene: SMARCD2 was added gene: SMARCD2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMARCD2 were set to 28369036; 28369034 Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2, MIM# 617475; Neutropaenia; Neurodevelopmental abnormalities in some; Myelodysplasia Review for gene: SMARCD2 was set to GREEN Added comment: Three unrelated families and functional data. Sources: Expert list |
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| Mendeliome v0.1950 | TNFRSF9 |
Zornitza Stark gene: TNFRSF9 was added gene: TNFRSF9 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TNFRSF9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNFRSF9 were set to 30872117; 31501153 Phenotypes for gene: TNFRSF9 were set to EBV lymphoproliferation; B-cell lymphoma; Chronic active EBV infection Review for gene: TNFRSF9 was set to GREEN Added comment: Six unrelated individuals, two with same homozygous G109S missense variant, functional data. Sources: Expert list |
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| Mendeliome v0.1947 | CTPS1 | Zornitza Stark Mode of inheritance for gene: CTPS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1946 | JAK1 |
Zornitza Stark gene: JAK1 was added gene: JAK1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: JAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JAK1 were set to 28111307 Phenotypes for gene: JAK1 were set to Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections Review for gene: JAK1 was set to RED Added comment: Single family reported (mother and two children) with GoF variant. Sources: Expert list |
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| Mendeliome v0.1944 | IL2RB |
Zornitza Stark gene: IL2RB was added gene: IL2RB was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL2RB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL2RB were set to 31040184; 31040185 Phenotypes for gene: IL2RB were set to Immunodeficiency 63 with lymphoproliferation and autoimmunity, MIM# 618495; Lymphoproliferation, lymphadenopathy, hepatosplenomegaly, autoimmune haemolytic anaemia, dermatitis, enteropathy, hypergammaglobulinaemia, recurrent viral (EBV, CMV) infections Review for gene: IL2RB was set to GREEN Added comment: Five families reported. Sources: Expert list |
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| Mendeliome v0.1943 | AP3D1 |
Zornitza Stark gene: AP3D1 was added gene: AP3D1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP3D1 were set to 26744459; 9697856 Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050; Oculocutaneous albinism; Severe neutropaenia; Recurrent infections; Seizures; Hearing loss; Neurodevelopmental delay Review for gene: AP3D1 was set to RED Added comment: Single family and a mouse model. Sources: Expert list |
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| Mendeliome v0.1942 | FAAP24 |
Zornitza Stark gene: FAAP24 was added gene: FAAP24 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FAAP24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAAP24 were set to 27473539 Phenotypes for gene: FAAP24 were set to EBV infection-driven lymphoproliferative disease Review for gene: FAAP24 was set to RED Added comment: Single sib pair with homozygous missense variant, some functional data. Sources: Expert list |
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| Mendeliome v0.1941 | SH3KBP1 | Zornitza Stark Tag SV/CNV tag was added to gene: SH3KBP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1941 | SH3KBP1 |
Zornitza Stark gene: SH3KBP1 was added gene: SH3KBP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SH3KBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SH3KBP1 were set to 29636373; 21708930 Phenotypes for gene: SH3KBP1 were set to Immunodeficiency 61, MIM# 300310 Review for gene: SH3KBP1 was set to RED Added comment: Single family reported, 247.5-kb intragenic deletion detected by array. Sources: Expert list |
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| Mendeliome v0.1940 | ARHGEF1 |
Zornitza Stark gene: ARHGEF1 was added gene: ARHGEF1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARHGEF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARHGEF1 were set to 30521495 Phenotypes for gene: ARHGEF1 were set to Immunodeficiency 62, MIM#618459 Review for gene: ARHGEF1 was set to RED Added comment: Single family, functional data. Sources: Expert list |
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| Mendeliome v0.1937 | ATP6AP1 | Zornitza Stark Mode of inheritance for gene: ATP6AP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1936 | IRF2BP2 |
Zornitza Stark gene: IRF2BP2 was added gene: IRF2BP2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IRF2BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IRF2BP2 were set to 27016798 Phenotypes for gene: IRF2BP2 were set to Immunodeficiency, common variable, 14, MIM# 617765 Review for gene: IRF2BP2 was set to RED Added comment: Single family reported only. Sources: Expert list |
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| Mendeliome v0.1931 | SLC39A7 |
Zornitza Stark gene: SLC39A7 was added gene: SLC39A7 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC39A7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC39A7 were set to 30718914 Phenotypes for gene: SLC39A7 were set to Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia Review for gene: SLC39A7 was set to GREEN Added comment: Five unrelated families with hypomorphic variants and a mouse model recapitulating phenotype. Sources: Expert list |
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| Mendeliome v0.1929 | NFE2L2 |
Zornitza Stark gene: NFE2L2 was added gene: NFE2L2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NFE2L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NFE2L2 were set to 29018201 Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia, MIM# 617744; Recurrent respiratory and skin infection; Growth retardation; Developmental delay, borderline ID; White matter cerebral lesions Review for gene: NFE2L2 was set to GREEN Added comment: Four unrelated individuals reported. Sources: Expert list |
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| Mendeliome v0.1927 | ERBIN |
Zornitza Stark gene: ERBIN was added gene: ERBIN was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ERBIN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ERBIN were set to 28126831 Phenotypes for gene: ERBIN were set to Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some Review for gene: ERBIN was set to AMBER Added comment: Single family and functional data. Sources: Expert list |
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| Mendeliome v0.1925 | ZNF341 |
Zornitza Stark gene: ZNF341 was added gene: ZNF341 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ZNF341 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF341 were set to 29907691; 29907690 Phenotypes for gene: ZNF341 were set to Hyper-IgE recurrent infection syndrome 3, autosomal recessive, MIM# 618282; Mild facial dysmorphism; Early onset eczema; Recurrent bacterial skin infections, abscesses; Recurrent respiratory infections, lung abscesses and pneumothoraces; Hyperextensible joints, bone fractures, retention of primary teeth Review for gene: ZNF341 was set to GREEN Added comment: 19 individuals from 10 families reported, some sharing the same homozygous variants (at least 4 different LoF variants reported). Sources: Expert list |
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| Mendeliome v0.1923 | IL6ST |
Zornitza Stark gene: IL6ST was added gene: IL6ST was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL6ST were set to 28747427; 30309848; 12370259; 16041381; 31914175 Phenotypes for gene: IL6ST were set to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response. Review for gene: IL6ST was set to GREEN Added comment: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association. Sources: Expert list |
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| Mendeliome v0.1920 | IL6R | Zornitza Stark Mode of inheritance for gene: IL6R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1917 | LIG1 |
Zornitza Stark gene: LIG1 was added gene: LIG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIG1 were set to 30395541 Phenotypes for gene: LIG1 were set to Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis Review for gene: LIG1 was set to GREEN Added comment: Five individuals from three families. Sources: Expert list |
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| Mendeliome v0.1916 | POLE2 |
Zornitza Stark gene: POLE2 was added gene: POLE2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: POLE2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLE2 were set to 26365386 Phenotypes for gene: POLE2 were set to Combined immunodeficiency; Lymphopaenia; Lack of TRECS, absent proliferation in response to antigens; Hypoglobulinaemia; Recurrent infections, disseminated BCG infections; Autoimmunity; Facial dysmorphism Review for gene: POLE2 was set to RED Added comment: Single family reported with homozygous splice site variant. Sources: Expert list |
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| Mendeliome v0.1914 | FCHO1 |
Zornitza Stark gene: FCHO1 was added gene: FCHO1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FCHO1 were set to 32098969; 30822429 Phenotypes for gene: FCHO1 were set to Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis Review for gene: FCHO1 was set to GREEN Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data. Sources: Expert list |
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| Mendeliome v0.1913 | REL |
Zornitza Stark gene: REL was added gene: REL was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: REL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: REL were set to 31103457 Phenotypes for gene: REL were set to Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity Review for gene: REL was set to RED Added comment: Single individual from consanguineous family reported with homozygous canonical splice site variant, no functional data. Sources: Expert list |
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| Mendeliome v0.1910 | TFRC | Zornitza Stark Mode of inheritance for gene: TFRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1907 | RELA |
Zornitza Stark gene: RELA was added gene: RELA was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RELA were set to 28600438; 29305315 Phenotypes for gene: RELA were set to Mucocutaneous ulceration, chronic, MIM# 618287; Impaired NFkB activation; reduced production of inflammatory cytokines; autoimmune cytopaenias Review for gene: RELA was set to AMBER Added comment: Two families reported, somewhat different phenotypes. Sources: Expert list |
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| Mendeliome v0.1905 | RELB |
Zornitza Stark gene: RELB was added gene: RELB was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RELB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RELB were set to 7834753; 26385063 Phenotypes for gene: RELB were set to Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections Review for gene: RELB was set to AMBER Added comment: Single family reported, functional data. Sources: Expert list |
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| Mendeliome v0.1902 | CD247 | Zornitza Stark Mode of inheritance for gene: CD247 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1900 | NSMCE2 |
Tiong Tan gene: NSMCE2 was added gene: NSMCE2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NSMCE2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSMCE2 were set to 25105364 Phenotypes for gene: NSMCE2 were set to SECKEL SYNDROME 10 Penetrance for gene: NSMCE2 were set to Complete Review for gene: NSMCE2 was set to AMBER Added comment: Biallelic hypomorphic variants in two unrelated women with microcephalic primordial dwarfism, insulin-resistant diabetes, fatty liver, and hypertriglyceridemia developing in childhood; and primary gonadal failure. Good quality functional evidence. No additional confirmatory cases since 2014 publication Sources: Literature |
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| Mendeliome v0.1897 | TRPA1 |
Zornitza Stark gene: TRPA1 was added gene: TRPA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPA1 were set to 20547126; 16564016; 21468319; 28314413; 24778270; 24564660; 20718100 Phenotypes for gene: TRPA1 were set to Episodic pain syndrome, familial, 1, MIM# 615040 Review for gene: TRPA1 was set to AMBER Added comment: Single family and a lot of functional data. Sources: Expert list |
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| Mendeliome v0.1896 | PLEKHA5 |
Tiong Tan gene: PLEKHA5 was added gene: PLEKHA5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLEKHA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLEKHA5 were set to 29805042 Phenotypes for gene: PLEKHA5 were set to cleft lip; cleft palate Penetrance for gene: PLEKHA5 were set to Complete Review for gene: PLEKHA5 was set to GREEN Added comment: Sources: Literature |
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| Mendeliome v0.1894 | CNKSR1 |
Zornitza Stark gene: CNKSR1 was added gene: CNKSR1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CNKSR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CNKSR1 were set to 30450701; 30237576; 21937992 Phenotypes for gene: CNKSR1 were set to Intellectual disability Review for gene: CNKSR1 was set to AMBER Added comment: Three families reported, two as part of large cohorts reporting multiple novel genes. Note the family reported in PMID 30450701 appears to be the same family as reported in PMID 21937992. Some functional data in PMID 30450701, including Drosophila model. Sources: Expert Review |
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| Mendeliome v0.1892 | FRMD4A |
Zornitza Stark gene: FRMD4A was added gene: FRMD4A was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FRMD4A were set to 25388005; 30214071 Phenotypes for gene: FRMD4A were set to Intellectual disability; microcephaly; Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819 Review for gene: FRMD4A was set to AMBER Added comment: Single Bedouin Israeli family reported with homozygous variant initially. Good segregation data. No functional data. Another family reported as part of a large consanguineous microcephaly cohort, different variant. Sources: Expert Review |
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| Mendeliome v0.1890 | NEK10 |
Zornitza Stark gene: NEK10 was added gene: NEK10 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: NEK10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEK10 were set to 31959991 Phenotypes for gene: NEK10 were set to Primary ciliary dyskinesia; bronchiectasis Review for gene: NEK10 was set to GREEN Added comment: Nine individuals from 5 unrelated families, some functional data. Sources: NHS GMS |
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| Mendeliome v0.1888 | PIGK |
Zornitza Stark gene: PIGK was added gene: PIGK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGK were set to 32220290 Phenotypes for gene: PIGK were set to Intellectual disability; seizures; cerebellar atrophy Review for gene: PIGK was set to GREEN Added comment: 12 individuals from 9 unrelated families reported. Sources: Literature |
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| Mendeliome v0.1886 | ADARB1 |
Zornitza Stark gene: ADARB1 was added gene: ADARB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADARB1 were set to 32220291 Phenotypes for gene: ADARB1 were set to Intellectual disability; microcephaly; seizures Review for gene: ADARB1 was set to GREEN Added comment: Four unrelated individuals with bi-allelic variants in this gene. Sources: Literature |
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| Mendeliome v0.1883 | HSPB3 | Zornitza Stark Mode of inheritance for gene: HSPB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1879 | FBXO38 | Zornitza Stark Mode of inheritance for gene: FBXO38 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1876 | DRP2 |
Zornitza Stark gene: DRP2 was added gene: DRP2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DRP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: DRP2 were set to 26227883; 11430802; 31217940; 22764250; 29473052 Phenotypes for gene: DRP2 were set to Charcot Marie Tooth, intermediate X-linked; HMSN Review for gene: DRP2 was set to GREEN Added comment: Three unrelated families, functional data. Sources: Expert list |
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| Mendeliome v0.1874 | DGAT2 |
Zornitza Stark gene: DGAT2 was added gene: DGAT2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: DGAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DGAT2 were set to 26786738 Phenotypes for gene: DGAT2 were set to axonal Charcot-Marie-Tooth disease Review for gene: DGAT2 was set to AMBER Added comment: Single family (father and son) reported, with supporting in vitro functional assays and a zebrafish model. Sources: Expert Review |
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| Mendeliome v0.1872 | ERLIN1 |
Bryony Thompson gene: ERLIN1 was added gene: ERLIN1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ERLIN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERLIN1 were set to 24482476 Phenotypes for gene: ERLIN1 were set to Spastic paraplegia 62 MIM#615681 Review for gene: ERLIN1 was set to GREEN Added comment: Three unrelated consanguineous families with early onset pure HSP. Sources: Expert list |
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| Mendeliome v0.1866 | ARID2 | Zornitza Stark Mode of inheritance for gene: ARID2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1863 | DYNC1H1 | Zornitza Stark Mode of pathogenicity for gene: DYNC1H1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1862 | DYNC1H1 | Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1859 | PQBP1 | Zornitza Stark Mode of pathogenicity for gene: PQBP1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1858 | PQBP1 | Zornitza Stark Mode of inheritance for gene: PQBP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1855 | CHD3 | Zornitza Stark Mode of pathogenicity for gene: CHD3 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1854 | CHD3 | Zornitza Stark Mode of inheritance for gene: CHD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1851 | DLG3 | Zornitza Stark Mode of inheritance for gene: DLG3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1847 | FBN2 | Zornitza Stark Mode of inheritance for gene: FBN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1845 | AGTPBP1 |
Zornitza Stark gene: AGTPBP1 was added gene: AGTPBP1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGTPBP1 were set to 30420557 Phenotypes for gene: AGTPBP1 were set to Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276 Review for gene: AGTPBP1 was set to GREEN Added comment: Thirteen individuals with bi-allelic variants in this gene, complex neurological phenotype of dev delay/ID, cerebellar atrophy and neuropathy, severe progressive course in six. Sources: NHS GMS |
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| Mendeliome v0.1841 | EIF2AK2 |
Zornitza Stark gene: EIF2AK2 was added gene: EIF2AK2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK2 were set to 32197074 Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness Review for gene: EIF2AK2 was set to GREEN Added comment: Eight individuals with de novo variants and complex neurodevelopmental phenotype. Sources: Literature |
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| Mendeliome v0.1840 | EIF2AK1 |
Zornitza Stark gene: EIF2AK1 was added gene: EIF2AK1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF2AK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK1 were set to 32197074 Phenotypes for gene: EIF2AK1 were set to Intellectual disability; white matter abnormalities Review for gene: EIF2AK1 was set to RED Added comment: Single individual reported with de novo variant in this gene. Sources: Literature |
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| Mendeliome v0.1838 | NOVA2 |
Zornitza Stark gene: NOVA2 was added gene: NOVA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NOVA2 were set to 32197073 Phenotypes for gene: NOVA2 were set to Intellectual disability; autism; hypotonia; spasticity; ataxia Mode of pathogenicity for gene: NOVA2 was set to Other Review for gene: NOVA2 was set to GREEN Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism. Sources: Literature |
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| Mendeliome v0.1836 | GNB2 |
Sue White gene: GNB2 was added gene: GNB2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GNB2 were set to 31698099 Phenotypes for gene: GNB2 were set to intellectual disability; dysmorphic features Penetrance for gene: GNB2 were set to Complete Review for gene: GNB2 was set to AMBER Added comment: single report of patient with de novo missense variant in GNB2 and intellectual disability. Emerging evidence of other de no missense variants in GNB2 and ID Sources: Literature |
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| Mendeliome v0.1834 | NRROS |
Sue White gene: NRROS was added gene: NRROS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NRROS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRROS were set to 32100099; 32197075 Phenotypes for gene: NRROS were set to neurodegeneration; intracranial calcification; epilepsy Penetrance for gene: NRROS were set to Complete Review for gene: NRROS was set to GREEN Added comment: normal development or mild developmental delay until onset of regression around age of 1 concurrent with epilepsy biallelic LOF mutations with functional evidence of pathogenicity Sources: Literature |
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| Mendeliome v0.1831 | CNOT3 | Zornitza Stark Mode of inheritance for gene: CNOT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1828 | CBS | Zornitza Stark Mode of inheritance for gene: CBS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1823 | SLC25A21 |
Zornitza Stark gene: SLC25A21 was added gene: SLC25A21 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: SLC25A21 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A21 were set to 29517768 Phenotypes for gene: SLC25A21 were set to Mitochondrial DNA depletion syndrome-18, MIM#618811 Review for gene: SLC25A21 was set to AMBER Added comment: One case with a homozygous variant and functional assays showing mitochondrial dysfunction. Sources: NHS GMS |
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| Mendeliome v0.1821 | SLC25A10 |
Zornitza Stark gene: SLC25A10 was added gene: SLC25A10 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: SLC25A10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A10 were set to 29211846 Phenotypes for gene: SLC25A10 were set to Intractable epileptic encephalopathy Review for gene: SLC25A10 was set to AMBER Added comment: One case with intractable epileptic encephalopathy with complex I deficiency, with biallelic variants. Yeast SLC25A10 ortholog lack-of-function causes impairment in mitochondrial respiration, reduced mtDNA copy number and oxidative stress vulnerability. Sources: NHS GMS |
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| Mendeliome v0.1817 | QARS | Zornitza Stark Mode of inheritance for gene: QARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1815 | PTCD3 |
Zornitza Stark gene: PTCD3 was added gene: PTCD3 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTCD3 were set to 30607703; 19427859 Phenotypes for gene: PTCD3 were set to Intellectual disability; optic atrophy; Leigh-like syndrome Review for gene: PTCD3 was set to AMBER Added comment: One compound heterozygote case and functional assays. Essential subunit of oxidative phosphorylation (OXPHOS) complexes. Sources: NHS GMS |
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| Mendeliome v0.1814 | PTCD1 |
Zornitza Stark gene: PTCD1 was added gene: PTCD1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: PTCD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTCD1 were set to 25058219 Phenotypes for gene: PTCD1 were set to Cardiomyopathy Review for gene: PTCD1 was set to RED Added comment: Single case reported with no functional characterisation. Biochemical analyses of heart tissue identified global COX defect. No OMIM phenotype. Sources: NHS GMS |
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| Mendeliome v0.1812 | PNPLA4 | Zornitza Stark Mode of inheritance for gene: PNPLA4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1809 | OXA1L |
Zornitza Stark gene: OXA1L was added gene: OXA1L was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: OXA1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OXA1L were set to 30201738; 16435202 Phenotypes for gene: OXA1L were set to Encephalopathy; hypotonia; developmental delay Review for gene: OXA1L was set to AMBER Added comment: Single family reported with biochemical and molecular analyses of patient skeletal muscle and fibroblasts. In vitro functional assays in human cell lines, Drosophila model, and yeast-based assays. Loss of function affects oxidative phosphorylation complexes IV and V. Sources: NHS GMS |
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| Mendeliome v0.1807 | NSUN3 |
Zornitza Stark gene: NSUN3 was added gene: NSUN3 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: NSUN3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSUN3 were set to 27356879 Phenotypes for gene: NSUN3 were set to combined mitochondrial respiratory chain complex deficiency Review for gene: NSUN3 was set to AMBER Added comment: A single compound heterozygous case. Patient-derived fibroblasts exhibited severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. In vitro functional assays also conducted. Sources: NHS GMS |
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| Mendeliome v0.1805 | NDUFB10 |
Zornitza Stark gene: NDUFB10 was added gene: NDUFB10 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: NDUFB10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFB10 were set to 28040730; 32025618 Phenotypes for gene: NDUFB10 were set to fatal infantile lactic acidosis; cardiomyopathy Review for gene: NDUFB10 was set to AMBER Added comment: Single compound heterozygote case and mitochondrial phenotype. Assays of respiratory chain enzyme activities and functions in patient tissues/fibroblasts and in vitro functional assays. Plant model system supporting mitochondrial complex I dysfunction. Sources: NHS GMS |
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| Mendeliome v0.1801 | MRM2 |
Zornitza Stark gene: MRM2 was added gene: MRM2 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRM2 were set to 28973171 Phenotypes for gene: MRM2 were set to MELAS-like Review for gene: MRM2 was set to AMBER Added comment: Single individual reported plus functional data. MRM2 encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA. Sources: NHS GMS |
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| Mendeliome v0.1798 | IDH3A |
Zornitza Stark gene: IDH3A was added gene: IDH3A was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: IDH3A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IDH3A were set to 31012789; 30478029; 30058936; 28412069 Phenotypes for gene: IDH3A were set to Retinitis pigmentosa Review for gene: IDH3A was set to GREEN Added comment: Six unrelated families reported with retinitis pigmentosa. Mouse model. Sources: NHS GMS |
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| Mendeliome v0.1797 | GATC |
Zornitza Stark gene: GATC was added gene: GATC was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: GATC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GATC were set to 30283131 Phenotypes for gene: GATC were set to Mitochondrial cardiomyopathy Review for gene: GATC was set to RED Added comment: Two families with 6 affected individuals reported; same homozygous variant. Sources: NHS GMS |
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| Mendeliome v0.1796 | GATB |
Zornitza Stark gene: GATB was added gene: GATB was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: GATB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GATB were set to 30283131 Phenotypes for gene: GATB were set to Mitochondrial cardiomyopathy Review for gene: GATB was set to RED Added comment: Single family reported with two affected siblings Sources: NHS GMS |
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| Mendeliome v0.1795 | FECH | Zornitza Stark Tag SV/CNV tag was added to gene: FECH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1793 | FECH | Zornitza Stark Mode of inheritance for gene: FECH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1792 | FECH | Zornitza Stark Tag deep intronic tag was added to gene: FECH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1790 | ADAM17 | Zornitza Stark Mode of inheritance for gene: ADAM17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1785 | ZNF462 | Zornitza Stark Mode of inheritance for gene: ZNF462 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1782 | HCFC1 | Zornitza Stark Mode of inheritance for gene: HCFC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1781 | TFAM |
Zornitza Stark gene: TFAM was added gene: TFAM was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TFAM were set to 27448789; 29021295; 9500544 Phenotypes for gene: TFAM were set to Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156 Review for gene: TFAM was set to AMBER Added comment: One consanguineous family segregates a homozygous variant. Tfam knockout mouse has a mitochondrial cardiomyopathy phenotype and severe mtDNA depletion with abolished oxidative phosphorylation. Sources: NHS GMS |
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| Mendeliome v0.1779 | TIMM22 |
Zornitza Stark gene: TIMM22 was added gene: TIMM22 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TIMM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMM22 were set to 30452684 Phenotypes for gene: TIMM22 were set to mitochondrial myopathy; hypotonia; gastroesophageal reflux disease Review for gene: TIMM22 was set to AMBER Added comment: One compound heterozygote case identified with supporting in vitro and patient cell functional assays. Sources: NHS GMS |
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| Mendeliome v0.1778 | TIMMDC1 | Zornitza Stark Tag deep intronic tag was added to gene: TIMMDC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1777 | TIMMDC1 |
Zornitza Stark gene: TIMMDC1 was added gene: TIMMDC1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMMDC1 were set to 28604674; 30981218 Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31 MIM#618251 Review for gene: TIMMDC1 was set to AMBER Added comment: A deep intronic variant (c.597-1340A>G, only detectable by WGS) that causes a splicing aberration was identified in a homozygous state in 3 unrelated cases from different ethnic backgrounds. A patient with Leigh-like syndrome had a homozygous stopgain variant in PDHX and a homozygous stopgain variant in TIMMDC1 (p.Arg225*). The TIMMDC1 mutant protein could still rescue complex I assembly in TIMMDC1 knockout cells and the patient’s clinical phenotype was not clearly distinct from that of other patients with the same PDHX defect. Sources: NHS GMS |
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| Mendeliome v0.1775 | TMEM65 |
Zornitza Stark gene: TMEM65 was added gene: TMEM65 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TMEM65 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM65 were set to 28295037 Phenotypes for gene: TMEM65 were set to Mitochondrial encephalomyopathy Review for gene: TMEM65 was set to AMBER Added comment: One homozygous case with a mitochondrial encephalomyopathy and functional assays showing the protein is important for mitochondrial respiration and mtDNA copy number maintenance. Sources: NHS GMS |
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| Mendeliome v0.1773 | SSBP1 |
Bryony Thompson gene: SSBP1 was added gene: SSBP1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: SSBP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SSBP1 were set to 31298765; 31479473; 31550237; 31550240 Phenotypes for gene: SSBP1 were set to Optic atrophy with or without extraocular phenotypes Review for gene: SSBP1 was set to GREEN Added comment: At least 9 dominant families/cases and 1 recessive with optic atrophy with/without additional clinical features, including retinal macular dystrophy, sensorineural deafness, mitochondrial myopathy, and kidney failure. Supporting evidence in functional assays and zebrafish model. Sources: NHS GMS |
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| Mendeliome v0.1771 | COX6A2 |
Zornitza Stark gene: COX6A2 was added gene: COX6A2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: COX6A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX6A2 were set to 31155743; 23460811 Phenotypes for gene: COX6A2 were set to Mitochondrial complex IV deficiency, MIM# 220110 Review for gene: COX6A2 was set to GREEN Added comment: Two unrelated families and two mouse models. Sources: Expert list |
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| Mendeliome v0.1769 | YME1L1 |
Zornitza Stark gene: YME1L1 was added gene: YME1L1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: YME1L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YME1L1 were set to 30544562; 27495975 Phenotypes for gene: YME1L1 were set to Optic atrophy 11, MIM#617302 Review for gene: YME1L1 was set to AMBER Added comment: One consanguineous family with a homozygous variant and functional assays. YME1L leads to mitochondrial fragmentation and severely disorganized and attenuated cristae architecture in in vitro functional assays. Sources: NHS GMS |
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| Mendeliome v0.1766 | ANXA11 |
Bryony Thompson gene: ANXA11 was added gene: ANXA11 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ANXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ANXA11 were set to 28469040; 29845112; 30109997 Phenotypes for gene: ANXA11 were set to Amytrophic lateral sclerosis 23 MIM#617839 Review for gene: ANXA11 was set to GREEN Added comment: 4 different missense variants in 10 patients from 7 unrelated families with amyotrophic lateral sclerosis and functional assays supporting association. Sources: Expert list |
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| Mendeliome v0.1763 | UQCRQ | Zornitza Stark Mode of inheritance for gene: UQCRQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1759 | UQCRC2 | Zornitza Stark Mode of inheritance for gene: UQCRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1755 | UQCC3 | Zornitza Stark Mode of inheritance for gene: UQCC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1751 | TXN2 | Zornitza Stark Mode of inheritance for gene: TXN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1747 | TARS2 | Zornitza Stark Mode of inheritance for gene: TARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1744 | SLC25A32 |
Zornitza Stark gene: SLC25A32 was added gene: SLC25A32 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A32 were set to 26933868; 28443623 Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive, MIM# 616839 Review for gene: SLC25A32 was set to GREEN Added comment: Two unrelated families reported with functional data. Muscle biopsy showed ragged-red fibers and lipid storage mainly in type I oxidative fibers, small type II fibers, and poor immunostaining for succinate dehydrogenase (FAD-dependent mitochondrial respiratory chain complex II). Oral supplementation with riboflavin led to dramatic improvement in the clinical and biologic abnormalities. Sources: Expert list |
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| Mendeliome v0.1741 | NFS1 | Zornitza Stark Mode of inheritance for gene: NFS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1737 | NDUFA6 | Zornitza Stark Mode of inheritance for gene: NDUFA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1734 | NDUFA4 | Zornitza Stark Mode of inheritance for gene: NDUFA4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1730 | NDUFA13 | Zornitza Stark Mode of inheritance for gene: NDUFA13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1727 | NADK2 |
Zornitza Stark gene: NADK2 was added gene: NADK2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NADK2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NADK2 were set to 24847004; 29388319; 27940755 Phenotypes for gene: NADK2 were set to 2,4-dienoyl-CoA reductase deficiency, MIM# 616034 Review for gene: NADK2 was set to GREEN gene: NADK2 was marked as current diagnostic Added comment: Mitochondrial dysfunction resulting in severe neurologic and metabolic dysfunction beginning in early infancy reported in two individuals with confirmed variants in this gene. Another individual with homozygous hypomorphic start loss variant g.36241900 A>G p. Met1Val and milder phenotype reported (PMID:29388319). Sources: Expert list |
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| Mendeliome v0.1725 | ISCA1 |
Zornitza Stark gene: ISCA1 was added gene: ISCA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISCA1 were set to 28356563; 32092383; 31016283; 30113620; 30105122 Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613 Review for gene: ISCA1 was set to GREEN gene: ISCA1 was marked as current diagnostic Added comment: Multiple unrelated families reported. Severe disorder characterised by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Rat model results in early lethality. Founder variant c.259G > A, p.(Glu87Lys) reported in Indian families. Sources: Expert list |
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| Mendeliome v0.1722 | ERCC5 | Zornitza Stark Mode of inheritance for gene: ERCC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1719 | BTD | Zornitza Stark Mode of inheritance for gene: BTD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1716 | CTNNB1 | Zornitza Stark Mode of pathogenicity for gene: CTNNB1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1715 | CTNNB1 | Zornitza Stark Mode of inheritance for gene: CTNNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1713 | ARL11 | Zornitza Stark Mode of inheritance for gene: ARL11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1709 | CLCN6 | Zornitza Stark Mode of inheritance for gene: CLCN6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1706 | SEMA6B |
Zornitza Stark gene: SEMA6B was added gene: SEMA6B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEMA6B were set to 32169168 Phenotypes for gene: SEMA6B were set to Progressive myoclonic epilepsy Mode of pathogenicity for gene: SEMA6B was set to Other Review for gene: SEMA6B was set to GREEN Added comment: Five individuals from unrelated families reported with de novo variants in the last exon, escaping NMD. Sources: Literature |
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| Mendeliome v0.1701 | CAMTA1 | Zornitza Stark Mode of inheritance for gene: CAMTA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1700 | CAMTA1 | Zornitza Stark Tag SV/CNV tag was added to gene: CAMTA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1699 | TNNI3K |
Zornitza Stark gene: TNNI3K was added gene: TNNI3K was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TNNI3K was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TNNI3K were set to 30010057; 29355681 Phenotypes for gene: TNNI3K were set to Cardiac conduction disease with or without dilated cardiomyopathy, MIM# 616117 Review for gene: TNNI3K was set to GREEN gene: TNNI3K was marked as current diagnostic Added comment: At least 6 multigenerational families reported where variants segregated with disease. Sources: Expert list |
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| Mendeliome v0.1696 | GPT2 | Zornitza Stark Mode of inheritance for gene: GPT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1693 | ERCC6L2 | Zornitza Stark Mode of inheritance for gene: ERCC6L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1690 | SUPT16H |
Zornitza Stark gene: SUPT16H was added gene: SUPT16H was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SUPT16H was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SUPT16H were set to 31924697 Phenotypes for gene: SUPT16H were set to Intellectual disability; Abnormality of the corpus callosum Review for gene: SUPT16H was set to GREEN Added comment: Four unrelated individuals with de novo missense variants in this gene. Publication also reports on a deletion, but note this includes other genes and the individual also had another CNV. Sources: Literature |
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| Mendeliome v0.1687 | RARS | Zornitza Stark Mode of inheritance for gene: RARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1684 | TNR |
Zornitza Stark gene: TNR was added gene: TNR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TNR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNR were set to 32099069 Phenotypes for gene: TNR were set to Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus Review for gene: TNR was set to GREEN Added comment: 13 individuals from 8 unrelated families reported. Sources: Literature |
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| Mendeliome v0.1681 | RSPRY1 | Zornitza Stark Mode of inheritance for gene: RSPRY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1677 | RPS23 | Zornitza Stark Mode of inheritance for gene: RPS23 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1676 | RPS23 | Zornitza Stark Mode of inheritance for gene: RPS23 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1667 | HMGA2 | Zornitza Stark Mode of inheritance for gene: HMGA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1666 | HMGA2 | Zornitza Stark Tag SV/CNV tag was added to gene: HMGA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1661 | MFSD2A | Zornitza Stark Mode of inheritance for gene: MFSD2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1659 | MED12L |
Zornitza Stark gene: MED12L was added gene: MED12L was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MED12L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MED12L were set to 31155615 Phenotypes for gene: MED12L were set to Intellectual disability; Seizures; Autism Review for gene: MED12L was set to GREEN Added comment: 7 individuals reported, 3 with CNVs (encompassing other genes) and 4 with SNVs (frameshift, nonsense and splice site). Sources: Expert list |
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| Mendeliome v0.1657 | MCM3AP |
Zornitza Stark gene: MCM3AP was added gene: MCM3AP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295 Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, MIM#618124 Review for gene: MCM3AP was set to GREEN gene: MCM3AP was marked as current diagnostic Added comment: At least 10 families reported. Sources: Expert list |
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| Mendeliome v0.1654 | MAPRE2 | Zornitza Stark Mode of inheritance for gene: MAPRE2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1651 | PURA | Zornitza Stark Mode of inheritance for gene: PURA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1648 | BPTF | Zornitza Stark Mode of inheritance for gene: BPTF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1645 | TRIO | Zornitza Stark Mode of inheritance for gene: TRIO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1642 | MAN1B1 | Zornitza Stark Mode of inheritance for gene: MAN1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1640 | KMT2C | Zornitza Stark Mode of inheritance for gene: KMT2C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1638 | GLRX5 | Zornitza Stark Mode of inheritance for gene: GLRX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1636 | NUDT2 |
Zornitza Stark gene: NUDT2 was added gene: NUDT2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUDT2 were set to 27431290; 30059600 Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability Review for gene: NUDT2 was set to AMBER Added comment: 7 affected individuals from 4 Saudi families, with same homozygous truncating variant. Sources: Expert list |
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| Mendeliome v0.1634 | NKAP |
Zornitza Stark gene: NKAP was added gene: NKAP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NKAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NKAP were set to 26358559; 26350204; 31587868 Phenotypes for gene: NKAP were set to Intellectual disability Review for gene: NKAP was set to GREEN gene: NKAP was marked as current diagnostic Added comment: 10 males from 8 unrelated families with missense mutations in NKAP (on Xq24) Hypotonia and tall stature with Marfanoid habitus was predominant phenotype. One variant (NM_024528:c.988G>A / p.Arg333Gln) Sources: Expert list |
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| Mendeliome v0.1631 | TBR1 | Zornitza Stark Mode of inheritance for gene: TBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1628 | GNRHR | Zornitza Stark Mode of inheritance for gene: GNRHR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1625 | MYO9A | Zornitza Stark Mode of inheritance for gene: MYO9A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1623 | ZDHHC15 | Zornitza Stark Mode of inheritance for gene: ZDHHC15 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1619 | ZBTB16 | Zornitza Stark Mode of inheritance for gene: ZBTB16 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1615 | ZBTB11 | Zornitza Stark Mode of inheritance for gene: ZBTB11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1611 | WNT3 | Zornitza Stark Mode of inheritance for gene: WNT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1607 | RS1 | Zornitza Stark Mode of inheritance for gene: RS1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1604 | SMC1A | Zornitza Stark Mode of inheritance for gene: SMC1A was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1602 | AIRE | Zornitza Stark Mode of pathogenicity for gene: AIRE was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1601 | AIRE | Zornitza Stark Mode of inheritance for gene: AIRE was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1600 | AIRE | Zornitza Stark Mode of inheritance for gene: AIRE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1597 | LOXHD1 | Zornitza Stark Mode of inheritance for gene: LOXHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1594 | WFS1 | Zornitza Stark Mode of inheritance for gene: WFS1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1589 | VARS | Zornitza Stark Mode of inheritance for gene: VARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1588 | KRT6A | Zornitza Stark Mode of pathogenicity for gene: KRT6A was changed from Other to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1585 | KRT6A | Zornitza Stark Mode of pathogenicity for gene: KRT6A was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1584 | KRT6A | Zornitza Stark Mode of inheritance for gene: KRT6A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1581 | TUBA8 | Zornitza Stark Mode of inheritance for gene: TUBA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1577 | RPL26 | Zornitza Stark Mode of inheritance for gene: RPL26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1572 | ABCC6 | Zornitza Stark Mode of inheritance for gene: ABCC6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1571 | ABCC6 | Zornitza Stark Mode of inheritance for gene: ABCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1568 | TRIM8 | Zornitza Stark Mode of inheritance for gene: TRIM8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1565 | TPH2 | Zornitza Stark Mode of inheritance for gene: TPH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1562 | SPOP |
Zornitza Stark gene: SPOP was added gene: SPOP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPOP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPOP were set to 32109420 Phenotypes for gene: SPOP were set to Intellectual disability; dysmorphism; microcephaly; macrocephaly Mode of pathogenicity for gene: SPOP was set to Other Review for gene: SPOP was set to GREEN Added comment: Seven individuals reported with de novo missense variants in this gene. Gain-of-function variants associated with microcephaly whereas dominant-negative variants associated with macrocephaly. Sources: Literature |
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| Mendeliome v0.1559 | TNIK | Zornitza Stark Mode of inheritance for gene: TNIK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1555 | TMLHE | Zornitza Stark Mode of inheritance for gene: TMLHE was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1553 | TMEM94 |
Zornitza Stark gene: TMEM94 was added gene: TMEM94 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM94 were set to 30526868 Phenotypes for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies, MIM#618316 Review for gene: TMEM94 was set to GREEN Added comment: 10 individuals from 6 unrelated families. Sources: Expert list |
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| Mendeliome v0.1550 | TMEM260 | Zornitza Stark Mode of inheritance for gene: TMEM260 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1546 | TKT | Zornitza Stark Mode of inheritance for gene: TKT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1542 | TELO2 | Zornitza Stark Mode of inheritance for gene: TELO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1539 | TECR | Zornitza Stark Mode of inheritance for gene: TECR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1535 | TBC1D7 | Zornitza Stark Mode of inheritance for gene: TBC1D7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1531 | TAF2 | Zornitza Stark Mode of inheritance for gene: TAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1527 | TAF13 | Zornitza Stark Mode of inheritance for gene: TAF13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1523 | SYT14 | Zornitza Stark Mode of inheritance for gene: SYT14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1519 | SRPX2 | Zornitza Stark Mode of inheritance for gene: SRPX2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1515 | SPRTN | Zornitza Stark Mode of inheritance for gene: SPRTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1512 | MC4R | Zornitza Stark Mode of inheritance for gene: MC4R was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1509 | KMT2A | Zornitza Stark Mode of inheritance for gene: KMT2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1506 | RBM20 | Zornitza Stark Mode of inheritance for gene: RBM20 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1503 | SLC52A1 | Zornitza Stark Mode of inheritance for gene: SLC52A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1498 | PTCH2 | Zornitza Stark Mode of inheritance for gene: PTCH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1494 | COL2A1 | Zornitza Stark Mode of inheritance for gene: COL2A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1491 | DNMT1 | Zornitza Stark Mode of inheritance for gene: DNMT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1488 | CEP135 | Zornitza Stark Mode of inheritance for gene: CEP135 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1486 | CYP21A2 | Zornitza Stark Tag SV/CNV tag was added to gene: CYP21A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1486 | CYP21A2 | Zornitza Stark Mode of inheritance for gene: CYP21A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1483 | CDK13 | Zornitza Stark Mode of inheritance for gene: CDK13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1480 | F13B | Zornitza Stark Mode of inheritance for gene: F13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1477 | FMO3 | Zornitza Stark Mode of inheritance for gene: FMO3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1474 | PNPLA6 | Zornitza Stark Mode of inheritance for gene: PNPLA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1473 | CEP85L |
Zornitza Stark gene: CEP85L was added gene: CEP85L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CEP85L were set to 32097630 Phenotypes for gene: CEP85L were set to Lissencephaly, posterior predominant Review for gene: CEP85L was set to GREEN Added comment: Thirteen individuals reported with mono allelic variants in this gene, inherited in two of the families. Mouse model had neuronal migration defects. Sources: Literature |
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| Mendeliome v0.1469 | SOBP | Zornitza Stark Mode of inheritance for gene: SOBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1465 | SNIP1 | Zornitza Stark Mode of inheritance for gene: SNIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1461 | SMG9 | Zornitza Stark Mode of inheritance for gene: SMG9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1458 | TMPRSS3 | Zornitza Stark Mode of inheritance for gene: TMPRSS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1455 | POU3F4 | Zornitza Stark Mode of inheritance for gene: POU3F4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1452 | SLIT2 | Zornitza Stark Mode of inheritance for gene: SLIT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1448 | CEL | Zornitza Stark Mode of inheritance for gene: CEL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1444 | WDR81 | Zornitza Stark Mode of inheritance for gene: WDR81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1443 | ARSG |
Zornitza Stark gene: ARSG was added gene: ARSG was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARSG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARSG were set to 29300381; 20679209; 25452429; 26975023 Phenotypes for gene: ARSG were set to Usher syndrome, type IV, MIM# 618144 Review for gene: ARSG was set to RED Added comment: Atypical late-onset RP/HL phenotype described in 5 individuals from three Yemenite Jewish families. Same homozygous missense variant identified in all, founder effect. Animal models associated with neuronal ceroid lipofuscinosis. Sources: Expert list |
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| Mendeliome v0.1440 | OTOF | Zornitza Stark Mode of inheritance for gene: OTOF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1438 | MYL1 |
Bryony Thompson gene: MYL1 was added gene: MYL1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYL1 were set to 30215711 Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy MIM#618414 Review for gene: MYL1 was set to AMBER Added comment: Two probands with congenital myopathy and a zebrafish model. Probably need one more family to push it over the line. Sources: NHS GMS |
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| Mendeliome v0.1436 | FXR1 |
Bryony Thompson gene: FXR1 was added gene: FXR1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: FXR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FXR1 were set to 30770808 Phenotypes for gene: FXR1 were set to Congenital multi-minicore myopathy Review for gene: FXR1 was set to GREEN Added comment: Two unrelated families and a mouse model with non-lethal myopathy phenotype. Sources: NHS GMS |
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| Mendeliome v0.1433 | TBCE | Zornitza Stark Mode of inheritance for gene: TBCE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1430 | HTRA1 | Zornitza Stark Mode of pathogenicity for gene: HTRA1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1429 | HTRA1 | Zornitza Stark Mode of inheritance for gene: HTRA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1426 | PLPBP | Zornitza Stark Mode of inheritance for gene: PLPBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1423 | PTPN11 | Zornitza Stark Mode of pathogenicity for gene: PTPN11 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1422 | PTPN11 | Zornitza Stark Mode of inheritance for gene: PTPN11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1419 | SYNE1 | Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1416 | PNPT1 | Zornitza Stark Mode of inheritance for gene: PNPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1410 | AANAT | Zornitza Stark Mode of inheritance for gene: AANAT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1408 | DUX4 | Zornitza Stark Tag SV/CNV tag was added to gene: DUX4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1407 | DUX4 | Zornitza Stark Mode of inheritance for gene: DUX4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1403 | SLC6A4 | Zornitza Stark Mode of inheritance for gene: SLC6A4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1399 | TREX1 | Zornitza Stark Mode of pathogenicity for gene: TREX1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1396 | HGSNAT | Zornitza Stark Mode of inheritance for gene: HGSNAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1393 | PNKP | Zornitza Stark Mode of inheritance for gene: PNKP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1390 | DNAH5 | Zornitza Stark Mode of inheritance for gene: DNAH5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1387 | CDH23 | Zornitza Stark Mode of inheritance for gene: CDH23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1384 | SHROOM4 | Zornitza Stark Mode of inheritance for gene: SHROOM4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1380 | F2 | Zornitza Stark Mode of inheritance for gene: F2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1379 | F2 | Zornitza Stark Tag 5'UTR tag was added to gene: F2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1378 | CHD2 | Zornitza Stark Mode of inheritance for gene: CHD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1375 | INTS1 | Zornitza Stark Mode of inheritance for gene: INTS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1370 | SOX3 | Zornitza Stark Mode of inheritance for gene: SOX3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1368 | SOX3 | Zornitza Stark Tag SV/CNV tag was added to gene: SOX3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1368 | AKT1 | Zornitza Stark Mode of inheritance for gene: AKT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1366 | AKT1 | Zornitza Stark Tag somatic tag was added to gene: AKT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1365 | AKT1 | Zornitza Stark Mode of pathogenicity for gene: AKT1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1362 | PEX6 | Zornitza Stark Mode of inheritance for gene: PEX6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1360 | PUF60 | Zornitza Stark Mode of inheritance for gene: PUF60 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1358 | ATRX | Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1356 | PTRHD1 |
Zornitza Stark gene: PTRHD1 was added gene: PTRHD1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PTRHD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTRHD1 were set to 30398675; 27134041; 27753167; 29143421 Phenotypes for gene: PTRHD1 were set to Parkinsonism; Intellectual disability Review for gene: PTRHD1 was set to GREEN Added comment: Three unrelated families reported: two with homozygous missense variants; and one with truncating variant. Affected individuals have juvenile-onset parkinsonism and ID. Sources: Expert list |
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| Mendeliome v0.1353 | GFER | Zornitza Stark Mode of inheritance for gene: GFER was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1350 | KRT14 | Zornitza Stark Mode of pathogenicity for gene: KRT14 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1349 | KRT14 | Zornitza Stark Mode of inheritance for gene: KRT14 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1346 | PITRM1 |
Zornitza Stark gene: PITRM1 was added gene: PITRM1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PITRM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PITRM1 were set to 26697887; 29764912; 29383861 Phenotypes for gene: PITRM1 were set to Ataxia; Intellectual disability Review for gene: PITRM1 was set to GREEN gene: PITRM1 was marked as current diagnostic Added comment: Three unrelated families reported with bi-allelic variants in this gene. Sources: Expert list |
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| Mendeliome v0.1344 | CSGALNACT1 |
Tiong Tan gene: CSGALNACT1 was added gene: CSGALNACT1 was added to Mendeliome. Sources: Expert Review,Literature Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CSGALNACT1 were set to Congenital disorders of glycosylation; skeletal dysplasia; advanced bone age Review for gene: CSGALNACT1 was set to GREEN Added comment: Two unrelated families and functional studies Sources: Expert Review, Literature |
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| Mendeliome v0.1341 | UNC13A | Zornitza Stark Mode of inheritance for gene: UNC13A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1338 | TOR1AIP1 |
Bryony Thompson gene: TOR1AIP1 was added gene: TOR1AIP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937 Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072 Review for gene: TOR1AIP1 was set to GREEN Added comment: At least 5 families/cases reported with muscular dystrophy and sometimes cardiomyopathy. Sources: Expert list |
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| Mendeliome v0.1335 | EML1 | Zornitza Stark Mode of inheritance for gene: EML1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1333 | ELMO2 |
Zornitza Stark gene: ELMO2 was added gene: ELMO2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ELMO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ELMO2 were set to 27476657 Phenotypes for gene: ELMO2 were set to Vascular malformation, primary intraosseous, MIM#606893 Review for gene: ELMO2 was set to GREEN Added comment: Five unrelated families reported. Sources: Expert list |
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| Mendeliome v0.1325 | MAP3K20 |
Bryony Thompson gene: MAP3K20 was added gene: MAP3K20 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MAP3K20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAP3K20 were set to 27816943; 26755636 Phenotypes for gene: MAP3K20 were set to Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890 Review for gene: MAP3K20 was set to GREEN Added comment: 3 unrelated consanguineous families homozygous for 3 different variants with centronuclear myopathy, and at least 2 families reported with split-foot malformation. Null mouse model is embryonic lethal due to severe cardiac edema and growth retardation. Gene alias of ZAK used in the published studies. Sources: Expert list |
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| Mendeliome v0.1322 | PCDH10 | Zornitza Stark Mode of inheritance for gene: PCDH10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1318 | LNPK | Zornitza Stark Mode of inheritance for gene: LNPK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1314 | KIF4A | Zornitza Stark Mode of inheritance for gene: KIF4A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1310 | KCNK4 | Zornitza Stark Mode of pathogenicity for gene: KCNK4 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1309 | KCNK4 | Zornitza Stark Mode of inheritance for gene: KCNK4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1306 | INTS8 | Zornitza Stark Mode of inheritance for gene: INTS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1302 | SCO2 | Zornitza Stark Mode of inheritance for gene: SCO2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1299 | IDUA | Zornitza Stark Mode of inheritance for gene: IDUA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1296 | AHI1 | Zornitza Stark Mode of inheritance for gene: AHI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1293 | TGM5 | Zornitza Stark Mode of inheritance for gene: TGM5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1290 | PLEC | Zornitza Stark Mode of inheritance for gene: PLEC was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1287 | HSPG2 | Zornitza Stark Mode of inheritance for gene: HSPG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1286 | BEST1 | Zornitza Stark Mode of pathogenicity for gene: BEST1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1283 | BEST1 | Zornitza Stark Mode of inheritance for gene: BEST1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1280 | IGBP1 | Zornitza Stark Mode of inheritance for gene: IGBP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1276 | IQSEC2 | Zornitza Stark Mode of pathogenicity for gene: IQSEC2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1275 | IQSEC2 | Zornitza Stark Mode of inheritance for gene: IQSEC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1273 | GRIA1 |
Zornitza Stark gene: GRIA1 was added gene: GRIA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GRIA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178 Phenotypes for gene: GRIA1 were set to Intellectual disability; autism Review for gene: GRIA1 was set to GREEN Added comment: Multiple affected individuals reported but in large ID cohorts reporting multiple candidate genes. Recurrent (p.A636T) variant. Sources: Expert list |
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| Mendeliome v0.1270 | HDAC4 | Zornitza Stark Mode of pathogenicity for gene: HDAC4 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1268 | HDAC4 | Zornitza Stark Mode of inheritance for gene: HDAC4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1264 | UBR4 | Zornitza Stark Mode of inheritance for gene: UBR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1260 | GMNN | Zornitza Stark Mode of inheritance for gene: GMNN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1258 | TRAPPC4 |
Zornitza Stark gene: TRAPPC4 was added gene: TRAPPC4 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: TRAPPC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC4 were set to 31794024 Phenotypes for gene: TRAPPC4 were set to intellectual disability; epilepsy; spasticity; microcephaly Review for gene: TRAPPC4 was set to GREEN Added comment: Seven individuals from three unrelated families reported; recurrent splice site variant (hg19:chr11:g.118890966A>G; TRAPPC4: NM_016146.5; c.454+3A>G), not a founder variant. Sources: Expert Review |
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| Mendeliome v0.1256 | SNX27 |
Zornitza Stark gene: SNX27 was added gene: SNX27 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SNX27 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNX27 were set to 25894286; 31721175; 21300787; 23524343 Phenotypes for gene: SNX27 were set to intellectual disability; seizures Review for gene: SNX27 was set to GREEN Added comment: Three unrelated families and animal model. Sources: Expert Review |
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| Mendeliome v0.1254 | NSF |
Zornitza Stark gene: NSF was added gene: NSF was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NSF were set to 31675180 Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability Review for gene: NSF was set to AMBER Added comment: Two individuals reported with de novo missense variants in this gene. Sources: Literature |
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| Mendeliome v0.1252 | KAT8 |
Zornitza Stark gene: KAT8 was added gene: KAT8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KAT8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KAT8 were set to 31794431 Phenotypes for gene: KAT8 were set to Intellectual disability; seizures; autism; dysmorphic features Review for gene: KAT8 was set to GREEN Added comment: Eight unrelated individuals reported with de novo variants in this gene and a mouse model. All variants missense, in the chromobarrel domain or the acetyltransferase domain; three individuals had the same variant p.Tyr90Cys . One more individual reported with bi-allelic variants: one missense and one frameshift; carrier parents were normal suggesting that may be haploinsuffiency is not the mechanism. Sources: Literature |
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| Mendeliome v0.1249 | GABBR2 | Zornitza Stark Mode of inheritance for gene: GABBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1245 | HNRNPU | Zornitza Stark Mode of inheritance for gene: HNRNPU was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1243 | SERPINI1 | Zornitza Stark Mode of inheritance for gene: SERPINI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1240 | TTC7A | Zornitza Stark Mode of inheritance for gene: TTC7A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1238 | OPA1 | Zornitza Stark Mode of inheritance for gene: OPA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1235 | SASS6 | Zornitza Stark Mode of inheritance for gene: SASS6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1231 | ACTB | Sebastian Lunke Mode of pathogenicity for gene: ACTB was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1230 | ACTB | Sebastian Lunke Mode of inheritance for gene: ACTB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1226 | GCKR | Sebastian Lunke Mode of inheritance for gene: GCKR was changed from Unknown to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1222 | CNTN1 | Zornitza Stark Mode of inheritance for gene: CNTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1218 | NDUFA12 | Zornitza Stark Mode of inheritance for gene: NDUFA12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1214 | MRPS7 | Zornitza Stark Mode of inheritance for gene: MRPS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1210 | MRPS23 | Zornitza Stark Mode of inheritance for gene: MRPS23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1208 | MRPL12 | Zornitza Stark Mode of inheritance for gene: MRPL12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1202 | LYRM4 | Zornitza Stark Mode of inheritance for gene: LYRM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1198 | COX8A | Zornitza Stark Mode of inheritance for gene: COX8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1194 | COA5 | Zornitza Stark Mode of inheritance for gene: COA5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1191 | CLCN5 | Zornitza Stark Mode of inheritance for gene: CLCN5 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1189 | PHEX | Zornitza Stark Mode of inheritance for gene: PHEX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1186 | EHMT1 | Zornitza Stark Mode of inheritance for gene: EHMT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1183 | FIBP | Zornitza Stark Mode of inheritance for gene: FIBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1179 | CHST8 | Zornitza Stark Mode of inheritance for gene: CHST8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1177 | RASA2 | Sebastian Lunke Mode of inheritance for gene: RASA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1174 | TKFC |
Zornitza Stark gene: TKFC was added gene: TKFC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TKFC were set to 32004446 Phenotypes for gene: TKFC were set to Developmental delay; cataracts; liver dysfunction Review for gene: TKFC was set to AMBER Added comment: Two unrelated individuals reported. Sources: Literature |
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| Mendeliome v0.1172 | RALGAPA1 |
Zornitza Stark gene: RALGAPA1 was added gene: RALGAPA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RALGAPA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RALGAPA1 were set to 32004447 Phenotypes for gene: RALGAPA1 were set to Intellectual disability; hypotonia; infantile spasms. Review for gene: RALGAPA1 was set to GREEN Added comment: Four unrelated individuals reported. Sources: Literature |
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| Mendeliome v0.1169 | EPB41L1 | Zornitza Stark Mode of inheritance for gene: EPB41L1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1165 | EMC1 | Zornitza Stark Mode of inheritance for gene: EMC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1163 | SOD2 | Zornitza Stark Mode of inheritance for gene: SOD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1159 | ATAD3A | Zornitza Stark Mode of inheritance for gene: ATAD3A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1158 | ATAD3A | Zornitza Stark Tag SV/CNV tag was added to gene: ATAD3A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1156 | MYOM1 | Zornitza Stark Mode of inheritance for gene: MYOM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1152 | DLG4 | Zornitza Stark Mode of inheritance for gene: DLG4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1148 | DIP2B | Zornitza Stark Mode of pathogenicity for gene: DIP2B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1147 | DIP2B | Zornitza Stark Mode of inheritance for gene: DIP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1144 | DCPS |
Zornitza Stark gene: DCPS was added gene: DCPS was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DCPS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DCPS were set to 25701870; 30289615; 25712129 Phenotypes for gene: DCPS were set to Al-Raqad syndrome, MIM#616459 Review for gene: DCPS was set to GREEN gene: DCPS was marked as current diagnostic Added comment: 7 individuals from 3 families reported. Sources: Expert list |
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| Mendeliome v0.1142 | CUX1 |
Zornitza Stark gene: CUX1 was added gene: CUX1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CUX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CUX1 were set to 25059644; 20510857; 30014507 Phenotypes for gene: CUX1 were set to Global developmental delay with or without impaired intellectual development, 618330 Review for gene: CUX1 was set to GREEN gene: CUX1 was marked as current diagnostic Added comment: Nine individuals from 7 families reported. Three individuals had normal intelligence at school age despite significant early developmental delay. Sources: Expert list |
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| Mendeliome v0.1139 | COA3 | Zornitza Stark Mode of inheritance for gene: COA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1135 | CNTN3 | Zornitza Stark Mode of inheritance for gene: CNTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1133 | CDK5R1 | Zornitza Stark Mode of inheritance for gene: CDK5R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1127 | LIPN | Zornitza Stark Mode of inheritance for gene: LIPN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1124 | SDR9C7 |
Zornitza Stark gene: SDR9C7 was added gene: SDR9C7 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SDR9C7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SDR9C7 were set to 28173123; 28369735 Phenotypes for gene: SDR9C7 were set to Ichthyosis, congenital, autosomal recessive 13 MIM#617574 Review for gene: SDR9C7 was set to GREEN Added comment: Three homozygous variants in 4 families with congenital ichthyosis. Sources: Expert list |
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| Mendeliome v0.1121 | ACSL4 | Zornitza Stark Mode of inheritance for gene: ACSL4 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1120 | RBBP8 | Zornitza Stark Added comment: Comment when marking as ready: Individuals from 3 families reported in the literature with bi-allelic variants in this gene: clinical diagnosis was Jawad syndrome in one, and Seckel syndrome in 2. ID is a reported feature. Additional variant in ClinVar, so overall rating Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1117 | RBBP8 | Zornitza Stark Mode of inheritance for gene: RBBP8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1115 | NIPBL | Zornitza Stark Mode of inheritance for gene: NIPBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1112 | HUWE1 | Zornitza Stark Mode of inheritance for gene: HUWE1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1109 | FLNA | Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1107 | WDR35 | Zornitza Stark Mode of inheritance for gene: WDR35 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1105 | DNAH11 | Zornitza Stark Mode of inheritance for gene: DNAH11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1103 | ELOVL1 | Zornitza Stark Mode of inheritance for gene: ELOVL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1101 | CLDN10 | Zornitza Stark Mode of inheritance for gene: CLDN10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1096 | CSTA | Zornitza Stark Mode of inheritance for gene: CSTA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1093 | CDSN | Zornitza Stark Mode of inheritance for gene: CDSN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1091 | CASP14 |
Zornitza Stark gene: CASP14 was added gene: CASP14 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CASP14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CASP14 were set to 27494380; 23014340; 17515931 Phenotypes for gene: CASP14 were set to Ichthyosis, congenital, autosomal recessive 12 MIM#617320 Review for gene: CASP14 was set to AMBER Added comment: The same 2bp deletion was identified in 3 patients with a mild form of generalised ichthyosis from 2 Algerian families. Casp14-/- mouse models had prominent dermatological features. Sources: Expert Review |
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| Mendeliome v0.1087 | ALDH3A2 | Zornitza Stark Mode of inheritance for gene: ALDH3A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1084 | ABHD5 | Zornitza Stark Mode of inheritance for gene: ABHD5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1081 | TUBGCP6 | Zornitza Stark Mode of inheritance for gene: TUBGCP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1078 | MYT1L | Zornitza Stark Mode of inheritance for gene: MYT1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1076 | LIPT1 | Zornitza Stark Mode of inheritance for gene: LIPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1074 | ARSA | Zornitza Stark Mode of inheritance for gene: ARSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1070 | ACTA1 | Zornitza Stark Mode of inheritance for gene: ACTA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||