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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 v0.2289 | 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 v0.2280 | KCNJ11 |
Elena Savva edited their review of gene: KCNJ11: Added comment: Congenital hyperinsulinism (HI) variants are generally reported in heterozygous patients where they also carry a somatic 2nd hit, or have isodisomy of the paternal allele (focal HI), or in bilallelic patients (diffuse HI). This condition can be dominant (but rarely), where patients with these missense are diazoxide-responsive. Patients with recessively inherited variants are diazoxide-unresponsive (OMIM, PMID:11395395, PMID: 23275527, PMID: 23345197). Genotype-phenotype correlation: Permanent neonatal diabetes – GOF (OMIM) Permanent neonatal diabetes + other features – GOF (OMIM) Congenital hyperinsulinism – LOF (PMID:18250167). PTCs - LOF Missense - Loss and gain of function LOF – cause reduce channel expression, channel activity and increase current decay (PMID:18250167) GOF - impair ATP-based sensitivity, more open state channel (OMIM) Mutations generally occur on the paternal allele (PMID: 23345197).; Changed publications: PMID:18250167, 11395395, 23275527, 23345197 |
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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 v0.2246 | PAX1 | Zornitza Stark changed review comment from: Note recent report of 6 individuals from three unrelated families with prominent immunological phenotype.; to: Note additional recent report of 6 individuals from three unrelated families with prominent immunological phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2204 | PPCS | Zornitza Stark changed review comment from: Five individuals from two unrelated families reported with missense variants. Functional studies in yeast to demonstrate impact of the variants on protein but not aimed at establishing gene-disease causation.; to: Five individuals from two unrelated families reported with missense variants. Functional studies in yeast to demonstrate impact of the variants on protein and cardiac dysfunction observed in Drosophila model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2200 | NUP188 | Zornitza Stark edited their review of gene: NUP188: Added comment: Additional 6 unrelated individuals with bi-allelic LoF variants reported, promoted to Green.; Changed rating: GREEN; Changed publications: 32021605, 28726809, 32275884; Changed phenotypes: microcephaly, ID, cataract, structural brain abnormalities, hypoventilation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.2013 | IL6ST |
Zornitza Stark changed review comment from: 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; to: 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. 2020: 12 individuals from 8 unrelated families with seven different mono-allelic truncating variants, dominant negative effect proposed. Sources: Expert list |
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| 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 v0.1985 | 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 v0.1974 | 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 v0.1964 | 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 v0.1955 | 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 v0.1952 | 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 v0.1933 | TOP2B |
Zornitza Stark changed review comment from: Association with deafness: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data. Association with immunological phenotypes: Four individuals from three unrelated families reported, all the variants affected the TOPRIM domain, functional data including mouse model. Sources: Literature; to: Association with deafness: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data. Association with immunological phenotypes: Four individuals from three unrelated families reported, all the variants affected the TOPRIM domain, functional data including mouse model. Intellectual disability: two unrelated individuals reported with same de novo variant, c.187C > T, p.(His63Tyr) and also supportive mouse model data. Sources: Literature |
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| Mendeliome v0.1932 | TOP2B |
Zornitza Stark changed review comment from: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data. Sources: Literature; to: Association with deafness: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data. Association with immunological phenotypes: Four individuals from three unrelated families reported, all the variants affected the TOPRIM domain, functional data including mouse model. Sources: Literature |
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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 v0.1913 | REL | Zornitza Stark Marked gene: REL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1913 | REL | Zornitza Stark Gene: rel has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1908 | RELA | Zornitza Stark Marked gene: RELA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1908 | RELA | Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1908 | RELA | Zornitza Stark Classified gene: RELA as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1908 | RELA | Zornitza Stark Gene: rela has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1906 | RELB | Zornitza Stark Marked gene: RELB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1906 | RELB | Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1906 | RELB | Zornitza Stark Classified gene: RELB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1906 | RELB | Zornitza Stark Gene: relb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1901 | NSMCE2 | Tiong Tan Added comment: Comment on list classification: Two unrelated women with good functional evidence; but no additional cases since 2014 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1890 | 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 v0.1876 | 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 v0.1872 | 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 v0.1857 | CHD3 | Zornitza Stark Added comment: Comment when marking as ready: Over 30 unrelated individuals reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1777 | 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 v0.1771 | 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 v0.1744 | 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 v0.1725 | 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 v0.1706 | 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 v0.1690 | 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 v0.1684 | 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 v0.1634 | 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 v0.1553 | 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 v0.1436 | 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 v0.1432 | HTRA1 | Zornitza Stark Phenotypes for gene: HTRA1 were changed from to {Macular degeneration, age-related, 7}, 6101493; {Macular degeneration, age-related, neovascular type}, 610149; CARASIL syndrome, 600142; Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1418 | SYNE1 |
Zornitza Stark edited their review of gene: SYNE1: Added comment: Well established gene-disease association with Emery-Dreifuss muscular dystrophy (AD), and with recessive ataxia. Distal arthrogryposis: three families reported with bi-allelic distal truncating variants in the KASH domain. This appears to be a specific genotype-phenotype correlation.; Changed rating: GREEN; Changed publications: 23352163, 27782104; Changed phenotypes: Arthrogryposis multiplex congenita, myogenic type, MIM# 618484, Emery-Dreifuss muscular dystrophy 4, autosomal dominant, MIM# 612998, Spinocerebellar ataxia, autosomal recessive 8, MIM# 610743; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.1415 | HTRA1 | Elena Savva reviewed gene: HTRA1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29895533, 19387015; Phenotypes: {Macular degeneration, age-related, 7}, 6101493, {Macular degeneration, age-related, neovascular type}, 610149, CARASIL syndrome, 600142, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1346 | 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 v0.1333 | 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 v0.1258 | 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 v0.1252 | 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 v0.1232 | ACTB | Sebastian Lunke Phenotypes for gene: ACTB were changed from to Baraitser-Winter syndrome 1 243310; ACTB-related neurodevelopment disorder | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1220 | ACTB | Melanie Marty reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29220674; Phenotypes: ?Dystonia, juvenile-onset 607371, Baraitser-Winter syndrome 1 243310, ACTB-related neurodevelopment disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1161 | ATAD3A | Zornitza Stark Phenotypes for gene: ATAD3A were changed from to Harel-Yoon syndrome, MIM# 617183 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1158 | ATAD3A | Zornitza Stark reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27640307, 32004445; Phenotypes: Harel-Yoon syndrome, MIM# 617183; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1150 | DLG4 | Zornitza Stark edited their review of gene: DLG4: Added comment: Four unrelated individuals reported.; Changed rating: GREEN; Changed publications: 27479843, 25123844, 19617690, 29460436, 23020937, 28135719; Changed phenotypes: Intellectual disability, Marfanoid habitus; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1069 | LIPE |
Kristin Rigbye gene: LIPE was added gene: LIPE was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: LIPE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIPE were set to 27862896; 25475467; 24848981 Phenotypes for gene: LIPE were set to Lipodystrophy, familial partial, type 6, 615980 Review for gene: LIPE was set to GREEN gene: LIPE was marked as current diagnostic Added comment: LIPE is confirmed to be associated with partial familial lipodystrophy in OMIM. There are 3 unrelated cases of patients with partial lipodystrophy with different loss of function variants in the LIPE gene. Sources: Expert list |
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| Mendeliome v0.1023 | FBXW11 |
Alison Yeung gene: FBXW11 was added gene: FBXW11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FBXW11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FBXW11 were set to PMID: 31402090 Phenotypes for gene: FBXW11 were set to Intellectual disability; developmental eye anomalies; digital anomalies Review for gene: FBXW11 was set to GREEN Added comment: Reported in >3 unrelated individuals Functional studies in zebrafish Sources: Literature |
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| Mendeliome v0.1020 | ANAPC1 |
Alison Yeung gene: ANAPC1 was added gene: ANAPC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ANAPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ANAPC1 were set to PMID: 31303264 Phenotypes for gene: ANAPC1 were set to Rothmund Thomson syndrome type 1, OMIM 618625 Review for gene: ANAPC1 was set to GREEN gene: ANAPC1 was marked as current diagnostic Added comment: 7 unrelated families reported Sources: Literature |
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| Mendeliome v0.1018 | RINT1 |
Alison Yeung gene: RINT1 was added gene: RINT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RINT1 were set to PMID: 31204009 Phenotypes for gene: RINT1 were set to Recurrent acute liver failure Review for gene: RINT1 was set to GREEN gene: RINT1 was marked as current diagnostic Added comment: three unrelated individuals reported Sources: Literature |
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| Mendeliome v0.991 | CTBP1 |
Zornitza Stark gene: CTBP1 was added gene: CTBP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CTBP1 were set to 27094857; 28955726; 31041561 Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, MIM#617915 Review for gene: CTBP1 was set to GREEN gene: CTBP1 was marked as current diagnostic Added comment: At least 12 unrelated individuals reported with this neurodevelopmental disorder. Sources: Expert list |
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| Mendeliome v0.981 | CCDC47 |
Sebastian Lunke gene: CCDC47 was added gene: CCDC47 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CCDC47 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC47 were set to 30401460 Phenotypes for gene: CCDC47 were set to Trichohepatoneurodevelopmental syndrome, 618268 Review for gene: CCDC47 was set to GREEN gene: CCDC47 was marked as current diagnostic Added comment: From GEL: Morimoto el al. (PMID: 30401460) report on 4 individuals from 4 unrelated families with biallelic LoF variants in CCDC47. The phenotype consisted of abnormal (woolly) hair, liver dysfunction, common facial features as well as DD/ID Sources: Expert list |
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| Mendeliome v0.975 | IKZF5 |
Zornitza Stark gene: IKZF5 was added gene: IKZF5 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: IKZF5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IKZF5 were set to 31217188 Phenotypes for gene: IKZF5 were set to Thrombocytopaenia Review for gene: IKZF5 was set to GREEN Added comment: Five unrelated individuals with missense variants in this gene. Two de novo, three segregated with disease Sources: Expert Review |
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| Mendeliome v0.973 | TTC12 |
Zornitza Stark gene: TTC12 was added gene: TTC12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TTC12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC12 were set to 31978331 Phenotypes for gene: TTC12 were set to Ciliary dyskinesia Review for gene: TTC12 was set to GREEN Added comment: Four unrelated families reported, LoF variants, respiratory phenotype. Sources: Literature |
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| Mendeliome v0.959 | PIGS |
Zornitza Stark gene: PIGS was added gene: PIGS was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGS were set to 30269814 Phenotypes for gene: PIGS were set to Glycosylphosphatidylinositol biosynthesis defect 18 618143 Review for gene: PIGS was set to GREEN Added comment: Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia to ID/EE Sources: Expert Review |
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| Mendeliome v0.957 | FUK |
Zornitza Stark gene: FUK was added gene: FUK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FUK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FUK were set to 30503518 Phenotypes for gene: FUK were set to Congenital disorder of glycosylation with defective fucosylation 2, MIM# 618324 Review for gene: FUK was set to AMBER Added comment: Two unrelated individuals reported. Sources: Literature |
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| Mendeliome v0.955 | ZNF142 |
Zornitza Stark gene: ZNF142 was added gene: ZNF142 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ZNF142 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF142 were set to 31036918 Phenotypes for gene: ZNF142 were set to Neurodevelopmental disorder with impaired speech and hyperkinetic movements, MIM#618425 Review for gene: ZNF142 was set to GREEN gene: ZNF142 was marked as current diagnostic Added comment: 7 individuals from 4 unrelated families reported. Sources: Expert list |
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| Mendeliome v0.953 | RALA |
Zornitza Stark gene: RALA was added gene: RALA was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RALA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RALA were set to 30500825 Phenotypes for gene: RALA were set to Intellectual disability; Seizures Review for gene: RALA was set to GREEN gene: RALA was marked as current diagnostic Added comment: 11 individuals from 10 unrelated families reported with this neurodevelopmental syndrome, half had seizures. Sources: Expert list |
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| Mendeliome v0.939 | HNRNPR |
Zornitza Stark gene: HNRNPR was added gene: HNRNPR was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HNRNPR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPR were set to 26795593; 31079900 Phenotypes for gene: HNRNPR were set to Intellectual disability; seizures Review for gene: HNRNPR was set to GREEN gene: HNRNPR was marked as current diagnostic Added comment: Five unrelated individuals reported with de novo variants and a neurodevelopmental disorder. Sources: Expert list |
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| Mendeliome v0.912 | DHPS |
Zornitza Stark gene: DHPS was added gene: DHPS was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DHPS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DHPS were set to 30661771 Phenotypes for gene: DHPS were set to Neurodevelopmental disorder with seizures and speech and walking impairment, MIM#618480 Review for gene: DHPS was set to GREEN gene: DHPS was marked as current diagnostic Added comment: 5 individuals from 4 unrelated families with biallelic pathogenic variants in DHPS, note one variant is recurrent (c.518A>G or p.Asn173Ser). The phenotype consisted of DD/ID (5/5), tone abnormalities (hypotonia/hypertonia/spasticity - 5/5), seizures (5/5 - in one case though unclear staring spells) with EEG abnormalities (5/5). Additionally most individuals displayed behavioral issues, or some common facial features Sources: Expert list |
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| Mendeliome v0.901 | PIK3C2A |
Zornitza Stark gene: PIK3C2A was added gene: PIK3C2A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PIK3C2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PIK3C2A were set to 31034465 Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome, MIM# 618440 Review for gene: PIK3C2A was set to GREEN gene: PIK3C2A was marked as current diagnostic Added comment: Three unrelated consanguineous families reported. Sources: Expert list |
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| Mendeliome v0.888 | MTHFS |
Zornitza Stark gene: MTHFS was added gene: MTHFS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTHFS were set to 30031689; 31844630; 22303332 Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367 Review for gene: MTHFS was set to GREEN Added comment: Three unrelated individuals reported with supporting biochemical evidence. Sources: Literature |
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| Mendeliome v0.876 | CDH2 |
Zornitza Stark gene: CDH2 was added gene: CDH2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDH2 were set to 31585109 Phenotypes for gene: CDH2 were set to Intellectual disability; corpus callosum abnormalities; congenital abnormalities Review for gene: CDH2 was set to GREEN Added comment: Nine unrelated individuals reported with de novo variants in this gene. Sources: Literature |
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| Mendeliome v0.870 | RPL13 |
Zornitza Stark gene: RPL13 was added gene: RPL13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RPL13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPL13 were set to 31630789 Phenotypes for gene: RPL13 were set to Spondyloepimetaphyseal Dysplasia with Severe Short Stature Review for gene: RPL13 was set to GREEN Added comment: Four unrelated individuals reported with de novo variants. Sources: Literature |
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| Mendeliome v0.865 | TUBGCP2 |
Zornitza Stark gene: TUBGCP2 was added gene: TUBGCP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TUBGCP2 were set to 31630790 Phenotypes for gene: TUBGCP2 were set to Lissencephaly; pachygyria; subcortical band heterotopia; microcephaly; intellectual disability Review for gene: TUBGCP2 was set to GREEN Added comment: Four unrelated families reported. Sources: Literature |
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| Mendeliome v0.860 | TP73 |
Alison Yeung gene: TP73 was added gene: TP73 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TP73 were set to PMID: 31130284 Phenotypes for gene: TP73 were set to Cortical malformation; Lissencephaly Review for gene: TP73 was set to AMBER Added comment: Two unrelated families reported. No functional data Sources: Literature |
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| Mendeliome v0.858 | SMG8 |
Alison Yeung gene: SMG8 was added gene: SMG8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SMG8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMG8 were set to PMID: 31130284 Phenotypes for gene: SMG8 were set to Intellectual disability Review for gene: SMG8 was set to AMBER Added comment: Two unrelated families reported. No functional data Sources: Literature |
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| Mendeliome v0.856 | IQSEC3 |
Alison Yeung gene: IQSEC3 was added gene: IQSEC3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IQSEC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IQSEC3 were set to PMID: 31130284 Phenotypes for gene: IQSEC3 were set to Intellectual disability Review for gene: IQSEC3 was set to AMBER Added comment: Two unrelated families reported, no functional data Sources: Literature |
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| Mendeliome v0.854 | ICE1 |
Alison Yeung gene: ICE1 was added gene: ICE1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ICE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ICE1 were set to PMID: 31130284 Phenotypes for gene: ICE1 were set to Intellectual disability, cerebral atrophy Review for gene: ICE1 was set to AMBER Added comment: Two unrelated families reported, no functional data Sources: Literature |
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| Mendeliome v0.852 | EIF2A |
Alison Yeung gene: EIF2A was added gene: EIF2A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EIF2A were set to PMID: 31130284 Phenotypes for gene: EIF2A were set to Intellectual disability, epilepsy Review for gene: EIF2A was set to AMBER Added comment: reported in two unrelated families Sources: Literature |
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| Mendeliome v0.844 | KCNN3 |
Alison Yeung gene: KCNN3 was added gene: KCNN3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNN3 were set to PMID: 31155282 Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3; OMIM# 618658 Review for gene: KCNN3 was set to GREEN gene: KCNN3 was marked as current diagnostic Added comment: Three unrelated individuals reported Sources: Literature |
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| Mendeliome v0.837 | CNOT1 |
Alison Yeung gene: CNOT1 was added gene: CNOT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNOT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CNOT1 were set to PMID: 31006513 Phenotypes for gene: CNOT1 were set to Holoprosencephaly 12, with or without pancreatic agenesis; OMIM# 618500 Review for gene: CNOT1 was set to GREEN gene: CNOT1 was marked as current diagnostic Added comment: Reported in 3 unrelated individuals Sources: Literature |
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| Mendeliome v0.835 | IQSEC1 |
Zornitza Stark gene: IQSEC1 was added gene: IQSEC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IQSEC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IQSEC1 were set to 31607425 Phenotypes for gene: IQSEC1 were set to Intellectual developmental disorder with short stature and behavioral abnormalities, MIM# 618687 Review for gene: IQSEC1 was set to GREEN Added comment: Five individuals from two unrelated families reported, animal model data. Sources: Literature |
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| Mendeliome v0.828 | LEMD2 |
Alison Yeung gene: LEMD2 was added gene: LEMD2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LEMD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: LEMD2 were set to PMID: 30905398 Phenotypes for gene: LEMD2 were set to progeroid disorder Review for gene: LEMD2 was set to AMBER Added comment: two reported unrelated individuals, limited functional evidence Sources: Literature |
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| Mendeliome v0.822 | FAM149B1 |
Alison Yeung gene: FAM149B1 was added gene: FAM149B1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM149B1 were set to PMID: 30905400 Phenotypes for gene: FAM149B1 were set to Joubert; Ciliopathy Review for gene: FAM149B1 was set to GREEN gene: FAM149B1 was marked as current diagnostic Added comment: Four unrelated families reported Sources: Literature |
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| Mendeliome v0.820 | CARS |
Alison Yeung gene: CARS was added gene: CARS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CARS were set to PMID: 30824121 Phenotypes for gene: CARS were set to Intellectual disability; microcephaly; brittle hair and nails Added comment: Three reported unrelated families Sources: Literature |
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| Mendeliome v0.814 | ADAMTS9 |
Zornitza Stark gene: ADAMTS9 was added gene: ADAMTS9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADAMTS9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS9 were set to 30609407 Phenotypes for gene: ADAMTS9 were set to Nephronophthisis-Related Ciliopathy Review for gene: ADAMTS9 was set to GREEN Added comment: Two families reported with functional evidence Sources: Literature |
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| Mendeliome v0.807 | BNC2 |
Zornitza Stark gene: BNC2 was added gene: BNC2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: BNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BNC2 were set to 31656805; 31051115 Phenotypes for gene: BNC2 were set to Lower urinary tract obstruction, congenital; OMIM #618612 Review for gene: BNC2 was set to GREEN gene: BNC2 was marked as current diagnostic Added comment: At least four unrelated families reported. Sources: Expert list |
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| Mendeliome v0.793 | STN1 |
Zornitza Stark gene: STN1 was added gene: STN1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STN1 were set to 27432940 Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcification and cysts 2, MIM#617341 Review for gene: STN1 was set to AMBER Added comment: Two unrelated individuals reported. Sources: Expert list |
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| Mendeliome v0.790 | JAM2 |
Zornitza Stark gene: JAM2 was added gene: JAM2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: JAM2 were set to 31851307 Phenotypes for gene: JAM2 were set to Primary brain calcification Review for gene: JAM2 was set to GREEN Added comment: Three unrelated families with bi-allelic variants reported. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages. Sources: Literature |
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| Mendeliome v0.788 | TDP2 |
Zornitza Stark gene: TDP2 was added gene: TDP2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: TDP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TDP2 were set to 31410782; 30109272; 24658003 Phenotypes for gene: TDP2 were set to Spinocerebellar ataxia, autosomal recessive 23; OMIM #616949 Review for gene: TDP2 was set to GREEN Added comment: ID is part of the phenotype: 4 families with 6 affected patients, with functional evidence. 1 family with 3 affected sibs with homozygous splice site mutation in the TDP2 gene. Patient cell extracts showed absence of the full-length TDP2 protein and absence of 5-prime TDP activity, consistent with a loss of function, although 3-prime TDP activity, conferred by TDP1, was normal. In addition, patient lymphoblastoid cells were hypersensitive to the TOP2 poison etoposide. The findings indicated impaired capacity for double-strand break repair. 1 unrelated Egyptian patient with a similar disorder was homozygous for a truncating mutation in the TDP2 gene 1 unrelated Caucasian patient with same homozygous splice site mutation in the TDP2 gene. Western blot analysis did not detect TDP2 protein in patient primary skin fibroblasts. Patient fibroblasts showed an inability to rapidly repair topoisomerase-induced DNA double-strand breaks in the nucleus and also showed a profound hypersensitivity to this type of DNA damage. Complementation of patient cells with recombinant human TDP2 restored normal rates of nuclear DSB repair. Sources: Expert list |
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| Mendeliome v0.786 | TRMT1 |
Zornitza Stark gene: TRMT1 was added gene: TRMT1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: TRMT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRMT1 were set to 30289604; 26308914; 21937992 Phenotypes for gene: TRMT1 were set to Mental retardation, autosomal recessive 68; OMIM #618302 Review for gene: TRMT1 was set to GREEN Added comment: 4 families reported: -1 consanguineous Iranian family with 5 individuals with nonsyndromic moderate to severe impaired intellectual development. -1 consanguineous Iranian family with 3 adult brothers with global developmental delay and moderately delayed intellectual development -2 unrelated Pakistani families with 4 patients with impaired intellectual development. All with homozygous mutations in the TRMT1 gene which segregated with the disorder in the families, but functional studies of the variants were not performed. Sources: Expert list |
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| Mendeliome v0.780 | SLC9A7 |
Zornitza Stark gene: SLC9A7 was added gene: SLC9A7 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SLC9A7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SLC9A7 were set to 30335141 Phenotypes for gene: SLC9A7 were set to Intellectual developmental disorder, X-linked 108; OMIM #301024 Review for gene: SLC9A7 was set to AMBER Added comment: 6 males from 2 unrelated families with hemizygous missense mutation in the SLC9A7 gene. The mutation segregated with the disorder in the family. In vitro functional expression studies in CHO cells (AP-1 cells) showed that the mutation caused decreased levels of protein expression and reduced oligosaccharide maturation/glycosylation compared to wildtype, indicating impaired posttranslational processing. Subcellular localization studies indicated that protein trafficking was unaffected by the mutation. However, examination of the trans-Golgi compartment suggested a gain-of-function effect and a perturbation of glycosylation of secretory cargo. Serum transferrin studies in 1 patient suggested a glycosylation defect. Sources: Literature |
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| Mendeliome v0.778 | KIAA1161 |
Zornitza Stark gene: KIAA1161 was added gene: KIAA1161 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: KIAA1161 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA1161 were set to 30656188; 30649222; 30460687; 29910000 Phenotypes for gene: KIAA1161 were set to Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317 Review for gene: KIAA1161 was set to GREEN Added comment: Total 9 families, but no functional evidence: 12 patients from 6 unrelated Chinese families reported by Yao et al. (2018) and homozygous or compound heterozygous mutations in the MYORG gene. Functional studies of the variants and studies of patient cells were not performed, but the presence of nonsense mutations suggested a loss of function. 1 Chinese woman identified with homozygous nonsense mutation in the MYORG gene, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. 2 unrelated Middle Eastern families with homozygous mutations in the MYORG gene, which segregated with the disorder in the families. Functional studies of the variants were not performed. 4 sibs from one Turkish family with homozygous missense mutation in the MYORG gene, which segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. Sources: Literature |
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| Mendeliome v0.748 | STAG2 |
Zornitza Stark gene: STAG2 was added gene: STAG2 was added to Mendeliome_VCGS. Sources: Other Mode of inheritance for gene: STAG2 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: STAG2 were set to 30765867; 28296084; 30447054; 29263825; 30158690 Phenotypes for gene: STAG2 were set to Mullegama-Klein-Martinez syndrome, MIM#301022 Review for gene: STAG2 was set to GREEN Added comment: 12 unrelated families reported both males and females affected. Sources: Other |
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| Mendeliome v0.723 | ITSN1 |
Zornitza Stark gene: ITSN1 was added gene: ITSN1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: ITSN1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ITSN1 were set to 29773874 Review for gene: ITSN1 was set to GREEN Added comment: 3 unrelated families with rare ITSN1 variants and SRNS/CNS or SSNS. Sources: Expert list |
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| Mendeliome v0.703 | AP2M1 |
Zornitza Stark gene: AP2M1 was added gene: AP2M1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: AP2M1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AP2M1 were set to 31104773 Phenotypes for gene: AP2M1 were set to Intellectual developmental disorder 60 with seizures, MIM# 618587 Review for gene: AP2M1 was set to GREEN Added comment: Four unrelated individuals reported, recurrent variant, NM_004068.3:c.508C>T or p.Arg170Trp. Sources: Expert list |
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| Mendeliome v0.671 | C19orf70 |
Zornitza Stark gene: C19orf70 was added gene: C19orf70 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: C19orf70 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C19orf70 were set to 29618761; 27623147; 27485409 Phenotypes for gene: C19orf70 were set to Combined oxidative phosphorylation deficiency 37, MIM# 618329 Review for gene: C19orf70 was set to GREEN Added comment: Three unrelated families reported. HGNC approved name MICOS13. Sources: Expert list |
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| Mendeliome v0.669 | MIPEP |
Zornitza Stark gene: MIPEP was added gene: MIPEP was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: MIPEP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIPEP were set to 27799064 Phenotypes for gene: MIPEP were set to Combined oxidative phosphorylation deficiency 31, MIM# 617228 Review for gene: MIPEP was set to GREEN Added comment: Four unrelated children reported. Sources: Expert list |
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| Mendeliome v0.667 | PLEKHG2 |
Zornitza Stark gene: PLEKHG2 was added gene: PLEKHG2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: PLEKHG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLEKHG2 were set to 26573021 Phenotypes for gene: PLEKHG2 were set to Leukodystrophy and acquired microcephaly with or without dystonia, MIM# 616763 Review for gene: PLEKHG2 was set to RED Added comment: Five individuals from two unrelated families reported, same homozygous missense variant. Sources: Expert list |
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| Mendeliome v0.660 | AIMP2 |
Zornitza Stark gene: AIMP2 was added gene: AIMP2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: AIMP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AIMP2 were set to 29215095 Phenotypes for gene: AIMP2 were set to Leukodystrophy, hypomyelinating, 17 618006 Review for gene: AIMP2 was set to RED Added comment: Two apparently unrelated consanguineous families, however same homozygous variant identified in both. Affected individuals had early-onset multifocal seizures, spasticity, poor overall growth, and microcephaly (up to -10 SD). Brain imaging showed multiple abnormalities, including cerebral and cerebellar atrophy, thin corpus callosum, abnormal signals in the basal ganglia, and features suggesting hypo- or demyelination Sources: Expert list |
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| Mendeliome v0.658 | TMEM63A |
Zornitza Stark gene: TMEM63A was added gene: TMEM63A was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: TMEM63A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TMEM63A were set to 31587869 Phenotypes for gene: TMEM63A were set to Leukodystrophy, hypomyelinating, 19, transient infantile, MIM# 618688 Review for gene: TMEM63A was set to GREEN Added comment: Four unrelated families reported; in three individuals, the variant was de novo, and inherited from a deceased parent in the fourth. Sources: Expert list |
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| Mendeliome v0.638 | RSRC1 |
Zornitza Stark gene: RSRC1 was added gene: RSRC1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: RSRC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RSRC1 were set to 28640246; 29522154 Phenotypes for gene: RSRC1 were set to Intellectual developmental disorder, autosomal recessive 70, MIM# 618402 Review for gene: RSRC1 was set to AMBER Added comment: Two unrelated families reported, 8 affected individuals. Sources: Expert list |
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| Mendeliome v0.636 | METTL5 |
Zornitza Stark gene: METTL5 was added gene: METTL5 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: METTL5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: METTL5 were set to 29302074; 31564433 Phenotypes for gene: METTL5 were set to Intellectual developmental disorder, autosomal recessive 72, MIM# 618665 Review for gene: METTL5 was set to GREEN Added comment: Three unrelated families and animal model. Sources: Expert list |
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| Mendeliome v0.633 | USP27X |
Zornitza Stark gene: USP27X was added gene: USP27X was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: USP27X was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: USP27X were set to 25644381 Phenotypes for gene: USP27X were set to Mental retardation, X-linked 105, MIM#300984 Review for gene: USP27X was set to AMBER Added comment: Four individuals from two unrelated families reported. Sources: Expert list |
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| Mendeliome v0.624 | TRPM3 |
Zornitza Stark gene: TRPM3 was added gene: TRPM3 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPM3 were set to 31278393 Phenotypes for gene: TRPM3 were set to Intellectual disability; epilepsy Review for gene: TRPM3 was set to GREEN Added comment: 8 unrelated individuals with de novo variants in this gene. Recurrent variant p.(Val837Met) identified in 7/8. Sources: Literature |
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| Mendeliome v0.610 | PIGP |
Zornitza Stark gene: PIGP was added gene: PIGP was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: PIGP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGP were set to 31139695 Phenotypes for gene: PIGP were set to Epileptic encephalopathy, early infantile, 55, MIM# 617599 Review for gene: PIGP was set to AMBER Added comment: Three individuals from two unrelated families reported. Sources: Expert list |
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| Mendeliome v0.608 | NEUROD2 |
Zornitza Stark gene: NEUROD2 was added gene: NEUROD2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: NEUROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NEUROD2 were set to 30323019 Phenotypes for gene: NEUROD2 were set to Epileptic encephalopathy, early infantile, 72, MIM# 618374 Review for gene: NEUROD2 was set to GREEN Added comment: Two unrelated individuals with de novo missense variants in this gene, animal model. Sources: Expert list |
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| Mendeliome v0.606 | GOT2 |
Zornitza Stark gene: GOT2 was added gene: GOT2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: GOT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GOT2 were set to 31422819 Phenotypes for gene: GOT2 were set to Epileptic encephalopathy, early infantile, 82, MIM# 618721 Review for gene: GOT2 was set to GREEN Added comment: Four individuals from three unrelated families reported. Treatment with pyridoxine and serine ameliorated the phenotype. Sources: Expert list |
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| Mendeliome v0.568 | PIGQ |
Zornitza Stark gene: PIGQ was added gene: PIGQ was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: PIGQ was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGQ were set to 25558065; 24463883; 31148362 Phenotypes for gene: PIGQ were set to Epileptic encephalopathy, early infantile, 77, MIM# 618548 Review for gene: PIGQ was set to GREEN Added comment: Three unrelated families reported. Sources: Expert list |
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| Mendeliome v0.563 | PHACTR1 |
Zornitza Stark gene: PHACTR1 was added gene: PHACTR1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: PHACTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PHACTR1 were set to 30256902 Phenotypes for gene: PHACTR1 were set to Epileptic encephalopathy, early infantile, 70, MIM# 618298 Review for gene: PHACTR1 was set to GREEN Added comment: Three unrelated individuals reported with de novo variants in this gene. Sources: Expert list |
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| Mendeliome v0.555 | CPLX1 |
Zornitza Stark gene: CPLX1 was added gene: CPLX1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: CPLX1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPLX1 were set to 26539891; 28422131 Phenotypes for gene: CPLX1 were set to Epileptic encephalopathy, early infantile, 63, MIM# 617976 Review for gene: CPLX1 was set to GREEN Added comment: Five individuals from three unrelated families reported in larger neurodevelopmental cohorts. Sources: Expert list |
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| Mendeliome v0.553 | RNF13 |
Zornitza Stark gene: RNF13 was added gene: RNF13 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: RNF13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RNF13 were set to 30595371 Phenotypes for gene: RNF13 were set to Epileptic encephalopathy, early infantile, 73, MIM# 618379 Mode of pathogenicity for gene: RNF13 was set to Other Review for gene: RNF13 was set to GREEN Added comment: Three unrelated individuals with de novo gain-of-function variants in this gene reported; severe neurodegenerative disorder, seizures are a prominent part of the phenotype. Sources: Literature |
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| Mendeliome v0.551 | GLS |
Zornitza Stark gene: GLS was added gene: GLS was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GLS were set to 30575854; 30970188 Phenotypes for gene: GLS were set to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412 Review for gene: GLS was set to GREEN Added comment: Three individuals from two unrelated families reported with early neonatal refractory seizures, structural brain abnormalities and oedema; significantly increased glutamine levels (PMID: 30575854). Another three unrelated individuals described with compound het variants, one of which is a triplet expansion in the 5' UTR (PMID: 30970188). Sources: Expert list |
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| Mendeliome v0.549 | CAD |
Zornitza Stark gene: CAD was added gene: CAD was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAD were set to 28007989; 25678555 Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50, MIM# 616457 Review for gene: CAD was set to GREEN Added comment: Five individuals from four unrelated families reported, seizures are a prominent part of the phenotype of this progressive neurometabolic condition. Sources: Expert list |
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| Mendeliome v0.541 | NADSYN1 |
Zornitza Stark gene: NADSYN1 was added gene: NADSYN1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NADSYN1 were set to 31883644 Phenotypes for gene: NADSYN1 were set to Multiple congenital abnormalities; absent kidneys; cardiac; limb; vertebral Review for gene: NADSYN1 was set to GREEN Added comment: Five individuals from four unrelated families. Sources: Literature |
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| Mendeliome v0.536 | UQCRFS1 |
Zornitza Stark gene: UQCRFS1 was added gene: UQCRFS1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: UQCRFS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UQCRFS1 were set to 31883641 Phenotypes for gene: UQCRFS1 were set to Mitochondrial Complex III deficiency; lactic acidosis; fetal bradycardia; hypertrophic cardiomyopathy; alopecia totalis Review for gene: UQCRFS1 was set to GREEN Added comment: Two unrelated families reported plus functional evidence. Sources: Literature |
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| Mendeliome v0.532 | WBP2 |
Zornitza Stark gene: WBP2 was added gene: WBP2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: WBP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WBP2 were set to 26881968 Phenotypes for gene: WBP2 were set to Deafness, autosomal recessive 107, MIM# 617639 Review for gene: WBP2 was set to AMBER Added comment: Two unrelated families identified in a large cohort; supportive animal model data. Sources: Expert list |
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| Mendeliome v0.529 | GRAP |
Zornitza Stark gene: GRAP was added gene: GRAP was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: GRAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GRAP were set to 30610177 Phenotypes for gene: GRAP were set to Deafness, autosomal recessive 114, MIM# 618456 Review for gene: GRAP was set to RED Added comment: Two apparently unrelated Turkish families reported, however same homozygous missense variant, and SNP analysis indicated identity by descent. Sources: Expert list |
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| Mendeliome v0.519 | PPIP5K2 |
Zornitza Stark gene: PPIP5K2 was added gene: PPIP5K2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: PPIP5K2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPIP5K2 were set to 29590114 Phenotypes for gene: PPIP5K2 were set to Deafness, autosomal recessive 100, MIM# 618422 Review for gene: PPIP5K2 was set to AMBER Added comment: Two apparently unrelated families with multiple affecteds segregating a homozygous missense variant; mouse model. Sources: Expert list |
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| Mendeliome v0.507 | AP1B1 |
Zornitza Stark gene: AP1B1 was added gene: AP1B1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP1B1 were set to 31630788; 31630791 Phenotypes for gene: AP1B1 were set to Intellectual disability; enteropathy; deafness; ichthyosis; keratoderma Review for gene: AP1B1 was set to GREEN Added comment: Four unrelated families with bi-allelic LoF variants in this gene. Sources: Literature |
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| Mendeliome v0.485 | DMXL2 |
Zornitza Stark gene: DMXL2 was added gene: DMXL2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: DMXL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DMXL2 were set to 31688942; 30237576 Phenotypes for gene: DMXL2 were set to Epileptic encephalopathy, early infantile, 81, MIM# 618663 Review for gene: DMXL2 was set to GREEN Added comment: Four unrelated families reported. Sources: Literature |
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| Mendeliome v0.479 | EPS8L2 |
Zornitza Stark gene: EPS8L2 was added gene: EPS8L2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: EPS8L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EPS8L2 were set to 26282398; 23918390; 28281779 Phenotypes for gene: EPS8L2 were set to Deafness autosomal recessive 106, MIM# 617637 Review for gene: EPS8L2 was set to GREEN Added comment: Two unrelated families and a mouse model. Sources: Expert list |
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| Mendeliome v0.460 | SLC5A6 |
Zornitza Stark gene: SLC5A6 was added gene: SLC5A6 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC5A6 were set to 31754459; 27904971 Phenotypes for gene: SLC5A6 were set to Developmental delay; epilepsy; neurodegeneration Review for gene: SLC5A6 was set to GREEN Added comment: Two unrelated families reported, functional data and some evidence of response to treatment. Sources: Literature |
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| Mendeliome v0.440 | COA7 |
Zornitza Stark gene: COA7 was added gene: COA7 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: COA7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COA7 were set to 29718187; 27683825 Phenotypes for gene: COA7 were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, MIM#618387 Review for gene: COA7 was set to GREEN Added comment: Five unrelated individuals reported with bi-allelic variants in this gene. Slowly progressive condition with variable onset, but at least three individuals presented at <5 years of age. Sources: Expert list |
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| Mendeliome v0.417 | NDUFAF8 |
Zornitza Stark gene: NDUFAF8 was added gene: NDUFAF8 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NDUFAF8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFAF8 were set to 31866046 Phenotypes for gene: NDUFAF8 were set to Leigh syndrome Review for gene: NDUFAF8 was set to GREEN Added comment: Three unrelated individuals with bi-allelic variants in this gene; functional data. Beware recurrent deep intronic splicing variant. Sources: Literature |
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| Mendeliome v0.415 | EEF1B2 |
Zornitza Stark gene: EEF1B2 was added gene: EEF1B2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: EEF1B2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EEF1B2 were set to 31845318; 21937992 Phenotypes for gene: EEF1B2 were set to Intellectual disability Review for gene: EEF1B2 was set to AMBER Added comment: 5 individuals from two unrelated families described in the literature so far, no functional data but gene belongs to a family implicated in neurodevelopmental disorders. Sources: Literature |
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| Mendeliome v0.399 | FLG2 |
Zornitza Stark gene: FLG2 was added gene: FLG2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: FLG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FLG2 were set to 29758285; 28884927; 29505760 Phenotypes for gene: FLG2 were set to Peeling skin syndrome 6, MIM# 618084 Review for gene: FLG2 was set to GREEN Added comment: 3 unrelated families reported. Sources: Literature |
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| Mendeliome v0.386 | NUP133 |
Zornitza Stark gene: NUP133 was added gene: NUP133 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NUP133 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP133 were set to 30179222 Phenotypes for gene: NUP133 were set to Nephrotic syndrome, type 18, MIM#618177 Review for gene: NUP133 was set to GREEN Added comment: Two unrelated families with functional data. Sources: Literature |
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| Mendeliome v0.383 | NUP85 |
Zornitza Stark gene: NUP85 was added gene: NUP85 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP85 were set to 30179222 Phenotypes for gene: NUP85 were set to Nephrotic syndrome, type 17, MIM#618176 Review for gene: NUP85 was set to GREEN Added comment: Three unrelated families reported. Sources: Literature |
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| Mendeliome v0.370 | KCNT2 |
Zornitza Stark gene: KCNT2 was added gene: KCNT2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNT2 were set to 29069600; 29740868 Phenotypes for gene: KCNT2 were set to Epileptic encephalopathy, early infantile, 57, MIM#617771; Developmental and epileptic encephalopathy Review for gene: KCNT2 was set to GREEN Added comment: Reviewed by E Palmer: Ambrosino et al described 2 unrelated females with de novo variants in KCNT2. The first patient had the variant p.(Arg190His) had with West syndrome followed by Lennox-Gastaut syndrome , the second patient had the variant p.(Arg190Pro) and DEE with migrating focal seizures. Both variants were absent gnomad and had supportive in silico support for pathogenicity. In an electrophisological model both KCNT2 R190P and KCNT2 R190H increased maximal current density and shifted toward more negative membrane potential values the activation curve of KCNT2 channels, consistent with gain of function effects. PMID: 29740868. Gururaj et al describe one male with de novo variant in KCNT2 p. (Phe240Leu) and early infantile epileptic encephalopathy. he variant was absent gnomad and supportive evidence of pathogenicity This variant was electrophysiologically modelled and revealed that the variant resulted in a 'change in function' demonstrating unusual altered selectivity in KNa channels.PMID: 29069600. Sources: Literature |
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| Mendeliome v0.366 | TASP1 |
Zornitza Stark gene: TASP1 was added gene: TASP1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: TASP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TASP1 were set to 31209944; 31350873 Phenotypes for gene: TASP1 were set to Developmental delay; microcephaly; dysmorphic features; congenital abnormalities Review for gene: TASP1 was set to GREEN Added comment: Four unrelated families reported; two with founder mutation. Protein interacts with KMT2A and KMT2D. Another infant with a de novo missense variant reported in a single infant with multiple congenital abnormalities, insufficient evidence for mono allelic disease at present. Sources: Literature |
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| Mendeliome v0.359 | MICB |
Sebastian Lunke changed review comment from: This gene is included in a large number of publications as it plays an central role immunity (MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I CHAIN-RELATED GENE B). However beyond a number of susceptibility associations, it does not appear to have been firmly associated with disease in patients.; to: This gene is included in a large number of publications as it plays an central role immunity (MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I CHAIN-RELATED GENE B). However beyond a number of susceptibility associations, it does not appear to have been firmly associated with disease in patients. https://ghr.nlm.nih.gov/gene/MICB#resources |
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| Mendeliome v0.338 | DEGS1 |
Zornitza Stark gene: DEGS1 was added gene: DEGS1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: DEGS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DEGS1 were set to 30620338; 30620337 Phenotypes for gene: DEGS1 were set to Leukodystrophy, hypomyelinating, 18, MIM#618404 Review for gene: DEGS1 was set to GREEN Added comment: 20 individuals from 14 unrelated families. Sources: Literature |
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| Mendeliome v0.333 | ZMIZ1 |
Zornitza Stark gene: ZMIZ1 was added gene: ZMIZ1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ZMIZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZMIZ1 were set to 30639322 Phenotypes for gene: ZMIZ1 were set to Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies; OMIM #618659 Review for gene: ZMIZ1 was set to GREEN Added comment: 19 unrelated individuals with heterozygous variants in this gene reported. Sources: Literature |
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| Mendeliome v0.331 | VAMP2 |
Zornitza Stark gene: VAMP2 was added gene: VAMP2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: VAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VAMP2 were set to 30929742 Phenotypes for gene: VAMP2 were set to Intellectual disability; Autism Review for gene: VAMP2 was set to GREEN Added comment: 5 unrelated patients with heterozygous de novo mutations in VAMP2, presenting with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. Sources: Literature |
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| Mendeliome v0.326 | TARS |
Zornitza Stark gene: TARS was added gene: TARS was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: TARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TARS were set to 31374204 Phenotypes for gene: TARS were set to Trichothiodystrophy 7, nonphotosensitive; OMIM #618546 Review for gene: TARS was set to AMBER Added comment: Clinical features of trichothiodystrophy (TTD) include ichthyosis, intellectual disability, decreased fertility, short stature. 2 unrelated patients with non-photosensitive-TTD, in whom limited clinical information was available (one with DD): one compound heterozygous TARS variants, second homozygous for TARS variant. They showed that the variants had a profound effect on TARS protein stability and enzymatic function. Sources: Literature |
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| Mendeliome v0.322 | SVBP |
Zornitza Stark gene: SVBP was added gene: SVBP was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SVBP were set to 31363758; 30607023 Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly; OMIM #618569 Review for gene: SVBP was set to GREEN Added comment: 5 unrelated families with homozygous mutations in SVBP. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls. Sources: Literature |
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| Mendeliome v0.315 | SCAPER |
Zornitza Stark gene: SCAPER was added gene: SCAPER was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SCAPER was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCAPER were set to 28794130; 31069901; 31192531; 30723319 Phenotypes for gene: SCAPER were set to Intellectual disability; retinitis pigmentosa Review for gene: SCAPER was set to GREEN Added comment: 28 patients from 14 unrelated families with ID and retinitis pigmentosa (some with BBS phenotype), and homozygous or compound heterozygous mutations in SCAPER gene. Sources: Literature |
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| Mendeliome v0.313 | SCAMP5 |
Zornitza Stark gene: SCAMP5 was added gene: SCAMP5 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SCAMP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SCAMP5 were set to 31439720 Phenotypes for gene: SCAMP5 were set to Intellectual disability; seizures; autism Mode of pathogenicity for gene: SCAMP5 was set to Other Review for gene: SCAMP5 was set to GREEN Added comment: 2 unrelated individuals with ASD, ID and seizures, with the same heterozygous de novo variant in SCAMP5 (p.Gly302Trp). Western blot analysis of proteins overexpressed in the Drosophila fat body showed strongly reduced levels of the SCAMP p.Gly302Trp protein compared with the wild-type protein, indicating that the mutant either reduced expression or increased turnover of the protein. The expression of the fly homologue of the human SCAMP5 p.Gly180Trp mutation caused similar eye and neuronal phenotypes as the expression of SCAMP RNAi, suggesting a dominant-negative effect. Sources: Literature |
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| Mendeliome v0.311 | PPP2CA |
Zornitza Stark gene: PPP2CA was added gene: PPP2CA was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PPP2CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PPP2CA were set to 30595372 Phenotypes for gene: PPP2CA were set to Neurodevelopmental disorder and language delay with or without structural brain abnormalities; OMIM #618354 Review for gene: PPP2CA was set to GREEN Added comment: 15 unrelated patients with a neurodevelopmental disorder with de novo heterozygous PPP2CA mutations, and 1 with partial deletion of PPP2CA. Functional studies showed complete PP2A dysfunction in 4 individuals with seemingly milder ID, hinting at haploinsufficiency. Ten other individuals showed mutation-specific biochemical distortions, including poor expression, altered binding to the A subunit and specific B-type subunits, and impaired phosphatase activity and C-terminal methylation. Sources: Literature |
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| Mendeliome v0.308 | PISD | Zornitza Stark commented on gene: PISD: 4 individuals in 2 unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature (Liberfarb syndrome). Affected individuals shared a homozygous 10-bp deletion immediately upstream of the last exon of the PISD gene. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts. 1 family with 2 sisters with congenital cataracts, short stature, and white matter changes identified compound heterozygous variants in the PISD gene. Decreased conversion of phosphatidylserine to PE in patient fibroblasts is consistent with impaired phosphatidylserine decarboxylase (PISD) enzyme activity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.307 | PIGB |
Zornitza Stark gene: PIGB was added gene: PIGB was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGB were set to 31256876 Phenotypes for gene: PIGB were set to Epileptic encephalopathy, early infantile, 80; OMIM #618580 Review for gene: PIGB was set to GREEN Added comment: 10 unrelated families with biallelic mutations in PIGB, with global DD and/or ID, and seizures. Two had polymicrogyria, 4 had a peripheral neuropathy, and 2 had a clinical diagnosis of DOORS syndrome. Patient lymphocytes and fibroblasts showed variably decreased levels of cell surface GPI-anchored proteins, including CD16 and CD59. In vitro functional expression studies performed with some of the mutations in PIGB-null CHO cells showed that the mutant proteins were unable to fully restore expression of GPI-anchored surface proteins, consistent with a loss of function, although the mutations had variable effects. Sources: Literature |
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| Mendeliome v0.305 | PIBF1 |
Zornitza Stark gene: PIBF1 was added gene: PIBF1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797 Phenotypes for gene: PIBF1 were set to Joubert syndrome 33; OMIM #617767 Review for gene: PIBF1 was set to GREEN Added comment: Three unrelated families plus three Hutterite families reported with bi-allelic variants in this gene. Sources: Literature |
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| Mendeliome v0.303 | PHF21A |
Zornitza Stark gene: PHF21A was added gene: PHF21A was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PHF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PHF21A were set to 31649809; 30487643; 22770980 Phenotypes for gene: PHF21A were set to Intellectual disability; dysmorphic features Review for gene: PHF21A was set to GREEN Added comment: 9 cases with intellectual disability and craniofacial anomalies (Potocki-Shaffer syndrome), with de novo truncating variants in PHF21A. No functional evidence of variants, but PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. 2 other unrelated individuals with translocations disrupting PHF21A. Lymphoblastoid cell lines from translocation subjects showed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional regulation. Sources: Literature |
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| Mendeliome v0.301 | POLR2A |
Sue White gene: POLR2A was added gene: POLR2A was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR2A were set to 31353023 Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MIM# 618603 Mode of pathogenicity for gene: POLR2A was set to Other Review for gene: POLR2A was set to GREEN Added comment: 11 unrelated individuals reported with de novo variants in this gene. Missense variants postulated to exert a dominant-negative effect; LoF variants by contrast resulted in milder phenotype. Sources: Literature |
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| Mendeliome v0.299 | PAK1 |
Zornitza Stark gene: PAK1 was added gene: PAK1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PAK1 were set to 31504246; 30290153 Phenotypes for gene: PAK1 were set to Intellectual developmental disorder with macrocephaly, seizures, and speech delay; OMIM #618158 Review for gene: PAK1 was set to GREEN Added comment: 2 unrelated individuals with de novo PAK1 mutations, with developmental delay, secondary macrocephaly, seizures, and ataxic gait. Enhanced phosphorylation of the PAK1 targets JNK and AKT shown in fibroblasts of one subject and of c-JUN in those of both subjects compared with control subjects. In fibroblasts of the 2 affected individuals, they observed a trend toward enhanced PAK1 kinase activity. By using co-immunoprecipitation and size-exclusion chromatography, they observed a significantly reduced dimerization for both PAK1 mutants compared with wild-type PAK1. 4 unrelated individuals with intellectual disability, macrocephaly and seizures, with de novo heterozygous missense variants in PAK1. Sources: Literature |
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| Mendeliome v0.294 | NFASC |
Zornitza Stark gene: NFASC was added gene: NFASC was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NFASC were set to 31501903; 28940097; 30124836; 30850329; 31608123 Phenotypes for gene: NFASC were set to Neurodevelopmental disorder with central and peripheral motor dysfunction; OMIM #618356 Review for gene: NFASC was set to GREEN Added comment: > 10 unrelated families reported, exhibiting a neurodevelopmental disorder (intellectual disability, developmental delay, motor impairment, speech difficulties, early onset demyelinating neuropathy), with homozygous variants in NFASC. Segregated with the disorder in the family. Some studies with functional evidence. Sources: Literature |
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| Mendeliome v0.288 | MAST1 |
Zornitza Stark gene: MAST1 was added gene: MAST1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAST1 were set to 31721002; 30449657 Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; OMIM #618273 Review for gene: MAST1 was set to GREEN Added comment: 6 unrelated patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) with de novo heterozygous mutations in MAST1 gene. In vitro functional studies showed that 1 of the variants (lys276del) increased MAST1 binding to microtubules compared to controls. Mutant mice heterozygous for a Mast1 leu278del allele showed a thicker corpus callosum compared to wildtype, and an overall reduction in cortical volume and thickness and decreased cerebellar volume and number of granule and Purkinje cells due to increased apoptosis compared to controls. 1 Emirati patient with ID, microcephaly, and dysmorphic features, with missense variant in MAST1. Sources: Literature |
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| Mendeliome v0.285 | LSS |
Zornitza Stark gene: LSS was added gene: LSS was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSS were set to 30723320 Phenotypes for gene: LSS were set to Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275; Intellectual disability Review for gene: LSS was set to GREEN Added comment: Expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. Ten APMR individuals from 6 unrelated families with biallelic variants in LSS. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. Sources: Literature |
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| Mendeliome v0.281 | KDM3B |
Zornitza Stark gene: KDM3B was added gene: KDM3B was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM3B were set to 30929739 Phenotypes for gene: KDM3B were set to Intellectual disability; dysmorphic features; short stature Review for gene: KDM3B was set to GREEN Added comment: 14 unrelated individuals and 3 affected parents with varying degrees of ID, DD, short stature, dysmorphism, and de novo or inherited pathogenic variants in KDM3B. No functional studies. Sources: Literature |
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| Mendeliome v0.279 | GRIA2 |
Zornitza Stark gene: GRIA2 was added gene: GRIA2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: GRIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GRIA2 were set to 31300657 Phenotypes for gene: GRIA2 were set to Intellectual disability; autism; Rett-like features; epileptic encephalopathy Review for gene: GRIA2 was set to GREEN Added comment: 28 unrelated patients with ID, ASD, Rett-like features, seizures/EE, and de novo heterozygous GRIA2 mutations. In functional expression studies, mutations led to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Sources: Literature |
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| Mendeliome v0.273 | GABRA5 |
Zornitza Stark gene: GABRA5 was added gene: GABRA5 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: GABRA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRA5 were set to 31056671; 29961870 Phenotypes for gene: GABRA5 were set to Epileptic encephalopathy, early infantile, 79; OMIM #618559 Review for gene: GABRA5 was set to GREEN Added comment: 3 unrelated patients with de novo heterozygous missense mutations in GABRA5 gene. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current. Sources: Literature |
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| Mendeliome v0.269 | FBXL3 |
Zornitza Stark gene: FBXL3 was added gene: FBXL3 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: FBXL3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FBXL3 were set to 30481285 Phenotypes for gene: FBXL3 were set to Intellectual developmental disorder with short stature, facial anomalies, and speech defects; OMIM #606220 Review for gene: FBXL3 was set to GREEN Added comment: Three unrelated families, multiple affected individuals. Sources: Literature |
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| Mendeliome v0.265 | EEF1D |
Zornitza Stark gene: EEF1D was added gene: EEF1D was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: EEF1D was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EEF1D were set to 30787422; 28097321 Phenotypes for gene: EEF1D were set to Intellectual disability Review for gene: EEF1D was set to AMBER Added comment: Two unrelated families reported; one as part of a very large cohort of consanguineous families reporting multiple new candidate genes. No functional data. Sources: Literature |
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| Mendeliome v0.263 | DYNC1I2 |
Zornitza Stark gene: DYNC1I2 was added gene: DYNC1I2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DYNC1I2 were set to 31079899 Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492 Review for gene: DYNC1I2 was set to GREEN Added comment: Five individuals from three unrelated families reported. Sources: Literature |
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| Mendeliome v0.256 | DDX6 |
Zornitza Stark gene: DDX6 was added gene: DDX6 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: DDX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DDX6 were set to 31422817 Phenotypes for gene: DDX6 were set to Intellectual developmental disorder with impaired language and dysmorphic facies, MIM#618653 Review for gene: DDX6 was set to GREEN Added comment: Five unrelated individuals reported with 5 different de novo heterozygous missense mutations in exon 11 of the DDX6 gene. All variants occurred at conserved residues in either the QxxR or V motifs within the second RecA-2 domain of the helicase core; this region is involved in RNA and/or ATP binding, suggesting functional consequences. Sources: Literature |
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| Mendeliome v0.247 | CDK8 |
Zornitza Stark gene: CDK8 was added gene: CDK8 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: CDK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDK8 were set to 30905399 Phenotypes for gene: CDK8 were set to Intellectual disability; dysmorphism; congenital abnormalities; seizures Review for gene: CDK8 was set to GREEN Added comment: 12 unrelated individuals, missense variants demonstrated as de novo in 10. All variants localize to the ATP-binding pocket of the kinase domain. Sources: Literature |
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| Mendeliome v0.233 | BRSK2 |
Zornitza Stark gene: BRSK2 was added gene: BRSK2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: BRSK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BRSK2 were set to 30879638 Phenotypes for gene: BRSK2 were set to Intellectual disability; autism Review for gene: BRSK2 was set to GREEN Added comment: Nine unrelated individuals with heterozygous variants in this gene; six confirmed de novo (parents available). Sources: Literature |
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| Mendeliome v0.231 | BCORL1 |
Zornitza Stark gene: BCORL1 was added gene: BCORL1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: BCORL1 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: BCORL1 were set to 24123876; 30941876 Phenotypes for gene: BCORL1 were set to Shukla-Vernon syndrome, MIM#301029 Review for gene: BCORL1 was set to GREEN Added comment: Four unrelated families reported altogether; some mothers mildly affected. Sources: Literature |
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| Mendeliome v0.229 | BCL11B |
Zornitza Stark gene: BCL11B was added gene: BCL11B was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: BCL11B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BCL11B were set to 29985992 Phenotypes for gene: BCL11B were set to Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities, MIM# 618092 Review for gene: BCL11B was set to GREEN Added comment: Nine unrelated individuals, all but one with de novo variants in this gene and syndromic ID/immunodeficiency. Most variants located in the last exon (exon 4) and are predicted to escape nonsense-mediated mRNA decay. Sources: Literature |
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| Mendeliome v0.224 | APC2 |
Zornitza Stark gene: APC2 was added gene: APC2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: APC2 were set to 31585108 Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10, MIM#618677 Review for gene: APC2 was set to GREEN Added comment: 12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum. Sources: Literature |
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| Mendeliome v0.220 | ACTL6B |
Zornitza Stark gene: ACTL6B was added gene: ACTL6B was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ACTL6B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACTL6B were set to 31134736; 31031012; 30656450; 30237576 Phenotypes for gene: ACTL6B were set to Epileptic encephalopathy, early infantile, 76, MIM# 618468; Intellectual developmental disorder with severe speech and ambulation defects, MIM# 618470 Review for gene: ACTL6B was set to GREEN Added comment: Over 10 unrelated individuals reported in the literature. Sources: Literature |
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| Mendeliome v0.215 | PPP1R21 |
Zornitza Stark gene: PPP1R21 was added gene: PPP1R21 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PPP1R21 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP1R21 were set to 30520571 Phenotypes for gene: PPP1R21 were set to Hypotonia; intellectual disability; white matter abnormalities Review for gene: PPP1R21 was set to GREEN Added comment: At least four unrelated families reported. Sources: Literature |
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| Mendeliome v0.167 | MIR17HG |
Zornitza Stark gene: MIR17HG was added gene: MIR17HG was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: MIR17HG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MIR17HG were set to 25391829; 21892160 Phenotypes for gene: MIR17HG were set to Feingold syndrome 2; OMIM #614326 Review for gene: MIR17HG was set to GREEN Added comment: 4 unrelated cases reported - 3 with gene deletions, 1 with SNV Sources: Expert list |
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| Mendeliome v0.165 | KLF7 |
Zornitza Stark gene: KLF7 was added gene: KLF7 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: KLF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLF7 were set to 29251763 Phenotypes for gene: KLF7 were set to Intellectual disability Review for gene: KLF7 was set to GREEN Added comment: Four unrelated individuals with de novo missense variants; animal model data supportive. Sources: Literature |
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| Mendeliome v0.148 | FRMPD4 |
Zornitza Stark gene: FRMPD4 was added gene: FRMPD4 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: FRMPD4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: FRMPD4 were set to 25644381; 29267967 Phenotypes for gene: FRMPD4 were set to Mental retardation, X-linked 104, MIM#300983 Review for gene: FRMPD4 was set to GREEN Added comment: Multiple affected individuals from unrelated families reported. Sources: Expert list |
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| Mendeliome v0.14 | KDM6B |
Zornitza Stark gene: KDM6B was added gene: KDM6B was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM6B were set to 31124279 Phenotypes for gene: KDM6B were set to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MIM#618505 Review for gene: KDM6B was set to GREEN Added comment: 12 unrelated patients reported with de novo variants in this gene, no functional evidence. Sources: Literature |
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| Mendeliome v0.0 | RELN |
Zornitza Stark gene: RELN was added gene: RELN was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: RELN was set to Unknown |
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| Mendeliome v0.0 | CRELD1 |
Zornitza Stark gene: CRELD1 was added gene: CRELD1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: CRELD1 was set to Unknown |
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