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| Mendeliome v0.3240 | KIAA1217 |
Zornitza Stark gene: KIAA1217 was added gene: KIAA1217 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIAA1217 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIAA1217 were set to 32369272 Phenotypes for gene: KIAA1217 were set to Vertebral anomalies, syndromic and non-syndromic Review for gene: KIAA1217 was set to AMBER Added comment: 10 families reported, however note only 3 of the variants were absent from gnomad, inheritance not reported, most variants are missense. Sources: Literature |
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| Mendeliome v0.3239 | RAP1GDS1 |
Zornitza Stark gene: RAP1GDS1 was added gene: RAP1GDS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAP1GDS1 were set to 32431071 Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features Review for gene: RAP1GDS1 was set to AMBER Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected. Sources: Literature |
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| Mendeliome v0.3231 | ADPRHL2 |
Zornitza Stark changed review comment from: Ataxia is part of the phenotype. Sources: Expert list; to: 14 families reported, onset is in the first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy. Sources: Expert list |
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| Mendeliome v0.3230 | GPR161 |
Zornitza Stark gene: GPR161 was added gene: GPR161 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GPR161 were set to 31609649 Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma Review for gene: GPR161 was set to GREEN Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue. Sources: Literature |
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| Mendeliome v0.3225 | ARF1 |
Zornitza Stark gene: ARF1 was added gene: ARF1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARF1 were set to 28868155 Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185 Review for gene: ARF1 was set to GREEN Added comment: Three unrelated individuals reported with de novo missense in this gene. Sources: Expert list |
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| Mendeliome v0.3222 | MRAS |
Zornitza Stark changed review comment from: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen. Sources: Expert list; to: Two unrelated individuals reported with de novo variants in this gene initially. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since. Sources: Expert list |
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| Mendeliome v0.3222 | MRAS |
Zornitza Stark gene: MRAS was added gene: MRAS was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MRAS were set to 28289718 Phenotypes for gene: MRAS were set to Noonan syndrome Review for gene: MRAS was set to AMBER Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen. Sources: Expert list |
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| Mendeliome v0.3216 | NRG1 |
Bryony Thompson gene: NRG1 was added gene: NRG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NRG1 were set to 22574178; 21706185; 28190554 Phenotypes for gene: NRG1 were set to Hirschsprung disease Review for gene: NRG1 was set to AMBER Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease. Sources: Expert list |
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| Mendeliome v0.3211 | CCDC32 | Zornitza Stark Added comment: Comment when marking as ready: Three affected individuals from two unrelated families, supportive animal model and other functional data consistent with this being a ciliopathy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3209 | PPP3R1 | Zornitza Stark Added comment: Comment when marking as ready: Currently just a locus; note multiple mouse models implicating a role for this gene in cardiovascular, renal and brain development. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3207 | CNRIP1 | Zornitza Stark Added comment: Comment when marking as ready: Currently just a locus, insufficient evidence for gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3202 | CAPZA2 |
Eleanor Williams gene: CAPZA2 was added gene: CAPZA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CAPZA2 were set to 32338762 Phenotypes for gene: CAPZA2 were set to intellectual disability Review for gene: CAPZA2 was set to AMBER Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles. Sources: Literature |
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| Mendeliome v0.3202 | PPP3R1 |
Eleanor Williams gene: PPP3R1 was added gene: PPP3R1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PPP3R1 were set to 32337552; 19159392 Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654 Review for gene: PPP3R1 was set to RED Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members. Sources: Literature |
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| Mendeliome v0.3202 | PLEK |
Eleanor Williams gene: PLEK was added gene: PLEK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PLEK were set to 32337552; 19159392 Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654 Review for gene: PLEK was set to RED Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members. Sources: Literature |
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| Mendeliome v0.3202 | CNRIP1 |
Eleanor Williams gene: CNRIP1 was added gene: CNRIP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CNRIP1 were set to 32337552; 19159392 Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654 Review for gene: CNRIP1 was set to RED Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members. Sources: Literature |
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| Mendeliome v0.3202 | CCDC32 |
Eleanor Williams gene: CCDC32 was added gene: CCDC32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC32 were set to 32307552 Phenotypes for gene: CCDC32 were set to craniofacial, cardiac and neurodevelopmental anomalies Review for gene: CCDC32 was set to AMBER Added comment: PMID: 32307552 - Harel et al 2020 - reports 2 unrelated consanguineous families with probands with homozygous frameshift variants in CCDC32. Parents are heterozygous. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development. Sources: Literature |
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| Mendeliome v0.3202 | SKIV2L | Zornitza Stark changed review comment from: Multiple families reported with trichohepatoenteric syndrome.; to: Multiple families reported with trichohepatoenteric syndrome, agree unclear if ID is an association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3198 | NLRP5 |
Zornitza Stark gene: NLRP5 was added gene: NLRP5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NLRP5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238 Phenotypes for gene: NLRP5 were set to Early embryonic arrest Review for gene: NLRP5 was set to AMBER Added comment: At least two families reported. Sources: Literature |
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| Mendeliome v0.3196 | EXOC7 |
Zornitza Stark gene: EXOC7 was added gene: EXOC7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC7 were set to 32103185 Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly Review for gene: EXOC7 was set to GREEN Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration. Sources: Literature |
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| Mendeliome v0.3195 | HNRNPH1 |
Zornitza Stark gene: HNRNPH1 was added gene: HNRNPH1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPH1 were set to 32335897; 29938792 Phenotypes for gene: HNRNPH1 were set to HNRNPH1‐related syndromic intellectual disability Review for gene: HNRNPH1 was set to GREEN Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant. 2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo. Sources: Literature |
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| Mendeliome v0.3194 | PDCD6IP |
Zornitza Stark gene: PDCD6IP was added gene: PDCD6IP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDCD6IP were set to 32286682 Phenotypes for gene: PDCD6IP were set to Microcephaly; intellectual disability Review for gene: PDCD6IP was set to AMBER Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies. Sources: Literature |
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| Mendeliome v0.3192 | NME5 |
Zornitza Stark gene: NME5 was added gene: NME5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NME5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NME5 were set to 32185794 Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia Review for gene: NME5 was set to AMBER Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy. Sources: Literature |
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| Mendeliome v0.3189 | EMILIN1 |
Naomi Baker changed review comment from: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein. Sources: Literature; to: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein. Sources: Literature |
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| Mendeliome v0.3189 | EMILIN1 |
Naomi Baker gene: EMILIN1 was added gene: EMILIN1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740. Phenotypes for gene: EMILIN1 were set to peripheral neuropathy Penetrance for gene: EMILIN1 were set to unknown Review for gene: EMILIN1 was set to AMBER Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein. Sources: Literature |
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| Mendeliome v0.3188 | ADAMTS3 |
Zornitza Stark gene: ADAMTS3 was added gene: ADAMTS3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS3 were set to 28985353; 30450763 Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154) Review for gene: ADAMTS3 was set to GREEN Added comment: Two families reported, supportive functional data. Sources: Expert list |
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| Mendeliome v0.3185 | MCM3AP | Eleanor Williams changed review comment from: PMID: 32202298 - Woldegebriel et al - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; to: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3185 | SP6 |
Eleanor Williams gene: SP6 was added gene: SP6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574 Phenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta Review for gene: SP6 was set to AMBER Added comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 ) Sources: Literature |
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| Mendeliome v0.3185 | MYH8 | Zornitza Stark Added comment: Comment when marking as ready: Recurrent variant p.R674Q has occurred de novo in at least some families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3182 | CACNB1 |
Zornitza Stark gene: CACNB1 was added gene: CACNB1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CACNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769 Phenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility Added comment: A single heterozygous case with a positive IVCT muscle biopsy has been reported with p.Val156Ala. The European non-Finnish allele frequency in gnomAD v2.1 is 0.001146 (148/129,118 alleles), which is higher than the expected population frequency for dominantly inherited malignant hyperthermia (0.1%). Additionally, functional assays of this variant, suggest it would only significantly affect function in the homozygous state (suggesting a recessive condition). Sources: Expert list |
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| Mendeliome v0.3174 | TSHZ1 | Zornitza Stark changed review comment from: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487).; to: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487). Also note original report contains four individuals with deletions of this gene, further supporting gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3164 | MT-TP | Bryony Thompson Added comment: Comment on list classification: This is a mitochondrial gene, which is on the Mitochondrial disease gene panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3156 | AXL |
Bryony Thompson gene: AXL was added gene: AXL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AXL were set to 18787040; 24476074 Phenotypes for gene: AXL were set to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism Review for gene: AXL was set to AMBER Added comment: Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P. Sources: Literature |
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| Mendeliome v0.3150 | GOLGA2 |
Elena Savva gene: GOLGA2 was added gene: GOLGA2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501 Phenotypes for gene: GOLGA2 were set to Nueromuscular disorder Review for gene: GOLGA2 was set to GREEN Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC. Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression. PMID: 26742501 - One infant with a homozygous PTC. Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization. Summary: 2 patients + animal model Sources: Expert list |
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| Mendeliome v0.3125 | FITM2 |
Bryony Thompson gene: FITM2 was added gene: FITM2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FITM2 were set to 28067622; 30214770; 30288795 Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness Review for gene: FITM2 was set to GREEN Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model. Sources: Expert list |
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| Mendeliome v0.3110 | STAG3 |
Bryony Thompson gene: STAG3 was added gene: STAG3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STAG3 were set to 24597867; 26059840; 31803224; 31363903 Phenotypes for gene: STAG3 were set to Premature ovarian failure 8 MIM#615723 Review for gene: STAG3 was set to GREEN Added comment: At least four unrelated families with ovarian failure and a supporting null mouse model. Sources: Expert list |
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| Mendeliome v0.3108 | SOHLH1 |
Bryony Thompson gene: SOHLH1 was added gene: SOHLH1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SOHLH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SOHLH1 were set to 25774885; 16690745; 31042289; 20506135; 28718531 Phenotypes for gene: SOHLH1 were set to Ovarian dysgenesis 5 MIM#617690; Spermatogenic failure 32 MIM#618115 Review for gene: SOHLH1 was set to GREEN Added comment: Women in 3 unrelated families with ovarian dysgenesis and homozygous variants, and a supporting null mouse model. At least 4 males with heterozygous variants and spermatogenic failure. Sources: Expert list |
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| Mendeliome v0.3106 | HFM1 |
Bryony Thompson gene: HFM1 was added gene: HFM1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: HFM1 were set to 23555294; 24597873; 31279343 Phenotypes for gene: HFM1 were set to Premature ovarian failure 9 MIM#615724 Review for gene: HFM1 was set to GREEN Added comment: Three cases from 2 unrelated families with compound heterozygous variants, and a single family with a heterozygous variant have been reported with ovarian failure. There is also a supporting null mouse model. Sources: Expert list |
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| Mendeliome v0.3088 | DCAF8 |
Bryony Thompson gene: DCAF8 was added gene: DCAF8 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DCAF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DCAF8 were set to 24500646 Phenotypes for gene: DCAF8 were set to Giant axonal neuropathy 2, autosomal dominant MIM#610100 Review for gene: DCAF8 was set to AMBER Added comment: A single large family segregating a missense variant and in vitro functional assays demonstrating the variant reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function Sources: Expert list |
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| Mendeliome v0.3086 | ARL6IP1 |
Bryony Thompson gene: ARL6IP1 was added gene: ARL6IP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARL6IP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARL6IP1 were set to 24482476; 31272422; 30980493; 28471035 Phenotypes for gene: ARL6IP1 were set to Spastic paraplegia 61, autosomal recessive MIM#615685 Review for gene: ARL6IP1 was set to GREEN gene: ARL6IP1 was marked as current diagnostic Added comment: At least 4 families reported with paediatric onset complicated spastic paraplegia and neuropathy. Supporting zebrafish model. Sources: Expert list |
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| Mendeliome v0.3084 | PMP2 |
Bryony Thompson gene: PMP2 was added gene: PMP2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PMP2 were set to 26257172; 26828946; 27009151 Phenotypes for gene: PMP2 were set to Charcot-Marie-Tooth disease, demyelinating, type 1G MIM#618279 Review for gene: PMP2 was set to GREEN Added comment: 4 unrelated families reported with missense variants, with supporting transgenic mouse and null zebrafish models. Sources: Expert list |
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| Mendeliome v0.3075 | SV2B |
Seb Lunke gene: SV2B was added gene: SV2B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SV2B was set to Unknown Publications for gene: SV2B were set to 23617838; 23937191 Phenotypes for gene: SV2B were set to seizures Review for gene: SV2B was set to RED Added comment: Multiply described in Epilepsy studies investigating role of SV2 gene family, however no patients directly attributed to variants in this gene and mouse models indicate viability without seizures. Sources: Literature Sources: Literature |
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| Mendeliome v0.3073 | RYR3 |
Zornitza Stark gene: RYR3 was added gene: RYR3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RYR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RYR3 were set to 29498452; 32451403; 31230720 Phenotypes for gene: RYR3 were set to Nemaline myopathy; fetal akinesia; arthrogryposis Review for gene: RYR3 was set to AMBER Added comment: One family reported with nemaline myopathy and other cases reported as part of large fetal akinesia/arthrogryposis discovery cohorts reporting multiple novel gene candidates. Sources: Expert list |
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| Mendeliome v0.3065 | HMGA2 | Zornitza Stark edited their review of gene: HMGA2: Added comment: At least four families reported with SNVs.; Changed rating: GREEN; Changed publications: 29655892, 25809938, 29453418, 29655892, 28796236; Changed phenotypes: Silver-Russel syndrome, MIM#618908 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3051 | TRIM69 |
Zornitza Stark gene: TRIM69 was added gene: TRIM69 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TRIM69 were set to 22105173 Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis Review for gene: TRIM69 was set to RED Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described. Sources: Expert list |
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| Mendeliome v0.3050 | LIMS2 |
Zornitza Stark gene: LIMS2 was added gene: LIMS2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: LIMS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIMS2 were set to 25589244; 16317048 Phenotypes for gene: LIMS2 were set to Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue MIM#616827 Review for gene: LIMS2 was set to RED Added comment: Only one family reported and Pinch2 -/- mice were viable and fertile with no apparent phenotype. Sources: Expert list |
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| Mendeliome v0.3048 | PSMB1 |
Zornitza Stark gene: PSMB1 was added gene: PSMB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMB1 were set to 32129449 Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly Review for gene: PSMB1 was set to AMBER Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model. Sources: Literature |
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| Mendeliome v0.3044 | C16orf62 |
Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475). Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251). Sources: Expert list |
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| Mendeliome v0.3037 | C16orf62 |
Zornitza Stark gene: C16orf62 was added gene: C16orf62 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C16orf62 were set to 25434475 Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome Review for gene: C16orf62 was set to AMBER Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475). Sources: Expert list |
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| Mendeliome v0.3028 | NUP88 |
Zornitza Stark gene: NUP88 was added gene: NUP88 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP88 were set to 30543681 Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393 Review for gene: NUP88 was set to GREEN Added comment: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model. Sources: Literature |
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| Mendeliome v0.3024 | RBL2 |
Zornitza Stark gene: RBL2 was added gene: RBL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RBL2 were set to 32105419; 9806916 Phenotypes for gene: RBL2 were set to Intellectual disability Review for gene: RBL2 was set to RED Added comment: Single family reported with pair of affected siblings. Supportive mouse model. Sources: Literature |
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| Mendeliome v0.3022 | GRM7 |
Zornitza Stark gene: GRM7 was added gene: GRM7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GRM7 were set to 32286009; 32248644 Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay Review for gene: GRM7 was set to GREEN Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model. Sources: Literature |
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| Mendeliome v0.3017 | PERP |
Zornitza Stark gene: PERP was added gene: PERP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PERP were set to 31898316 Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet Review for gene: PERP was set to AMBER Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible. Sources: Literature |
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| Mendeliome v0.3015 | ADCY6 |
Zornitza Stark gene: ADCY6 was added gene: ADCY6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADCY6 were set to 24319099; 26257172; 31846058 Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8, OMIM # 616287 Review for gene: ADCY6 was set to GREEN Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies. Sources: Literature |
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| Mendeliome v0.3014 | DSCR3 |
Zornitza Stark gene: DSCR3 was added gene: DSCR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DSCR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DSCR3 were set to 31845315 Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet Review for gene: DSCR3 was set to RED Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals. Sources: Literature |
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| Mendeliome v0.3013 | LEF1 |
Zornitza Stark gene: LEF1 was added gene: LEF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LEF1 were set to 32022899 Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet Review for gene: LEF1 was set to RED Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human. Sources: Literature |
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| Mendeliome v0.3010 | OTUD7A |
Zornitza Stark gene: OTUD7A was added gene: OTUD7A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OTUD7A were set to 31997314 Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet Review for gene: OTUD7A was set to RED Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies. Sources: Literature |
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| Mendeliome v0.2996 | ARL13B | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2996 | ARL13B | Zornitza Stark edited their review of gene: ARL13B: Added comment: Eight families reported in the literature. Many are homozygous missense variants in consanguineous families with no further supporting evidence, but sufficient number have functional evidence at protein level. Gene has appropriate tissue expression. Zebrafish model: curved tails and cystic kidneys. Hennin mouse model discovered in ENU mutagenesis screen: has polydactyly, ciliary defect, and much more severe neurological phenotype (neural tube defect).; Changed publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2987 | TTC5 |
Zornitza Stark gene: TTC5 was added gene: TTC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC5 were set to 29302074; 32439809 Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system Review for gene: TTC5 was set to GREEN Added comment: Eleven individuals from seven families reported. Sources: Literature |
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| Mendeliome v0.2977 | HIST1H4J |
Zornitza Stark gene: HIST1H4J was added gene: HIST1H4J was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HIST1H4J were set to 31804630 Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features Review for gene: HIST1H4J was set to AMBER Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype Sources: Literature |
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| Mendeliome v0.2971 | TOR1AIP1 | Zornitza Stark Added comment: Comment when marking as ready: Highly variable phenotype. Few of the features are consistently reported across affected individuals. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2965 | USP8 |
Bryony Thompson gene: USP8 was added gene: USP8 was added to Mendeliome. Sources: Expert list somatic tags were added to gene: USP8. Mode of inheritance for gene: USP8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: USP8 were set to 25675982; 24482476; 25485838; 25942478 Phenotypes for gene: USP8 were set to Pituitary adenoma 4, ACTH-secreting, somatic MIM#219090; hereditary spastic paraplegia Review for gene: USP8 was set to GREEN Added comment: Recurrent somatic gain of function missense variants in pituitary adenomas cause Cushing's disease. A single family reported with spastic paraplegia with a homozygous variant, and a zebrafish model with a movement disorder. Sources: Expert list |
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| Mendeliome v0.2959 | SCYL2 |
Zornitza Stark gene: SCYL2 was added gene: SCYL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCYL2 were set to 31960134; 26203146 Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome Review for gene: SCYL2 was set to AMBER Added comment: Two unrelated families reported with AMC, variable other features including microcephaly. Sources: Literature |
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| Mendeliome v0.2957 | VWA3B | Bryony Thompson Added comment: Comment on list classification: Single family and in vitro assay only | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2956 | RIMS2 |
Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness. Sources: Literature |
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| Mendeliome v0.2955 | VWA3B |
Bryony Thompson gene: VWA3B was added gene: VWA3B was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VWA3B were set to 26157035 Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948 Review for gene: VWA3B was set to AMBER Added comment: A homozygous missense variant was identified in 3 brothers from a single consanguineous Japanese family with autosomal recessive cerebellar ataxia. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability. Sources: Expert list |
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| Mendeliome v0.2953 | SOX6 |
Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo. Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome. Paper says 19 individuals from 17 families. 12 were de novo. Sources: Literature |
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| Mendeliome v0.2952 | SOX6 |
Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo. Sources: Literature |
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| Mendeliome v0.2950 | PLD3 |
Bryony Thompson gene: PLD3 was added gene: PLD3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PLD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLD3 were set to 29053796; 30312375; 30312384 Phenotypes for gene: PLD3 were set to Spinocerebellar ataxia 46 MIM#617770 Review for gene: PLD3 was set to AMBER Added comment: A heterozygous missense was identified in 8 affected members of a single family with spinocerebellar ataxia, and supporting in vitro functional assays. Sources: Expert list |
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| Mendeliome v0.2949 | SOX6 |
Paul De Fazio changed review comment from: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature |
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| Mendeliome v0.2949 | SPATA13 | Zornitza Stark Added comment: Comment when marking as ready: Adult-onset. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2944 | POC5 |
Bryony Thompson gene: POC5 was added gene: POC5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POC5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: POC5 were set to 25642776; 29272404 Phenotypes for gene: POC5 were set to Idiopathic scoliosis; retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis Review for gene: POC5 was set to GREEN Added comment: Three heterozygous missense variants identified in three families segregating with idiopathic scoliosis, and supporting zebrafish models for each of the missense variants. Also, one case reported with retinitis pigmentosa, short stature, microcephaly, and recurrent glomerulonephritis with a homozygous truncating variant and a supporting zebrafish model. Sources: Literature |
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| Mendeliome v0.2943 | KIF3B |
Paul De Fazio gene: KIF3B was added gene: KIF3B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly Review for gene: KIF3B was set to AMBER Added comment: 2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking. Sources: Literature |
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| Mendeliome v0.2943 | SPATA13 |
Ain Roesley changed review comment from: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp. Sources: Literature; to: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp. Sources: Literature |
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| Mendeliome v0.2943 | SPATA13 |
Ain Roesley gene: SPATA13 was added gene: SPATA13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPATA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPATA13 were set to PMID: 32339198 Phenotypes for gene: SPATA13 were set to primary angle-closure glaucoma Added comment: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp. Sources: Literature |
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| Mendeliome v0.2943 | SOX6 |
Paul De Fazio gene: SOX6 was added gene: SOX6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SOX6 were set to 32442410 Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature |
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| Mendeliome v0.2943 | CNP |
Kristin Rigbye gene: CNP was added gene: CNP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CNP were set to 32128616; 12590258 Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy Review for gene: CNP was set to AMBER Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling). Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts. Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family. Sources: Literature |
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| Mendeliome v0.2943 | RIMS2 |
Paul De Fazio changed review comment from: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Sources: Literature |
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| Mendeliome v0.2943 | TRIM71 |
Elena Savva gene: TRIM71 was added gene: TRIM71 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633 Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667 Mode of pathogenicity for gene: TRIM71 was set to Other Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child. PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism. Sources: Literature |
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| Mendeliome v0.2943 | RIMS2 |
Paul De Fazio gene: RIMS2 was added gene: RIMS2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RIMS2 were set to 32470375 Review for gene: RIMS2 was set to GREEN Added comment: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Sources: Literature |
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| Mendeliome v0.2942 | RBM7 |
Bryony Thompson gene: RBM7 was added gene: RBM7 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RBM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RBM7 were set to 27193168 Phenotypes for gene: RBM7 were set to SMA-like spinal motor neuropathy; dHMN/dSMA Review for gene: RBM7 was set to AMBER Added comment: Single case with a homozygote variant, with functional assays in patient fibroblasts. Also, supporting zebrafish model. Sources: Expert list |
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| Mendeliome v0.2940 | SORD |
Seb Lunke gene: SORD was added gene: SORD was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SORD were set to 32367058 Phenotypes for gene: SORD were set to isolated hereditary neuropathy Review for gene: SORD was set to GREEN gene: SORD was marked as current diagnostic Added comment: 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state Sources: Literature |
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| Mendeliome v0.2932 | DNAH6 |
Elena Savva gene: DNAH6 was added gene: DNAH6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DNAH6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH6 were set to PMID: 26918822 Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia Review for gene: DNAH6 was set to AMBER Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width. Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1. Summary: 1 convincing patient with animal model Sources: Literature |
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| Mendeliome v0.2926 | PRKAG3 | Bryony Thompson reviewed gene: PRKAG3: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 17878938, 10818001; Phenotypes: increased glycogen content in skeletal muscle; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2920 | MTMR14 | Bryony Thompson Added comment: Comment on list classification: No evidence of Mendelian disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2906 | SNRNP200 |
Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo |
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| Mendeliome v0.2906 | SNRNP200 |
Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD) PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA) PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo |
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| Mendeliome v0.2889 | ARL3 |
Bryony Thompson gene: ARL3 was added gene: ARL3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ARL3 were set to 30269812; 16565502; 26964041; 30932721 Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161; Retinitis pigmentosa 83 MIM#618173 Review for gene: ARL3 was set to GREEN Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina. Two unrelated families with retinitis pigmentosa segregating the same heterozygous missense variant (Y90C). Sources: Expert list |
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| Mendeliome v0.2882 | CEP19 |
Bryony Thompson gene: CEP19 was added gene: CEP19 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP19 were set to 29127258; 24268657 Phenotypes for gene: CEP19 were set to Morbid obesity and spermatogenic failure MIM#615703 Review for gene: CEP19 was set to AMBER Added comment: A consanguineous Arab family with morbid obesity and infertility with a homozygous predicted null variant, and a mouse model that recapitulates the phenotype. Another homozygous variant has been identified in a consanguineous Bardet Beidl syndrome. Sources: Literature |
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| Mendeliome v0.2880 | DALRD3 |
Zornitza Stark gene: DALRD3 was added gene: DALRD3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DALRD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DALRD3 were set to 32427860 Phenotypes for gene: DALRD3 were set to Epileptic encephalopathy Review for gene: DALRD3 was set to AMBER Added comment: Two individuals reported with same homozygous nonsense variant, functional data. Sources: Literature |
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| Mendeliome v0.2876 | KRAS | Zornitza Stark Phenotypes for gene: KRAS were changed from to Cardiofaciocutaneous syndrome 2 615278; Noonan syndrome 3 609942; RAS-associated autoimmune leukoproliferative disorder 614470; Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 163200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2867 | DHX30 | Zornitza Stark Added comment: Comment when marking as ready: Twelve unrelated individuals reported with de novo missense variants, some recurrent. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2861 | KRAS | Elena Savva reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23059812, 17056636; Phenotypes: Arteriovenous malformation of the brain, somatic 108010, Bladder cancer, somatic 109800, Breast cancer, somatic 114480, Cardiofaciocutaneous syndrome 2 615278, Gastric cancer, somatic 137215, Leukemia, acute myeloid 601626, . Lung cancer, somatic 211980, Noonan syndrome 3 609942, Pancreatic carcinoma, somatic 260350, RAS-associated autoimmune leukoproliferative disorder 614470, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 163200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2861 | FAT1 |
Ee Ming Wong changed review comment from: - 5 consanguineous families with homozygous frameshift mutations in FAN1 - FAN1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice - in human retinal pigment epithelium (RPE) cells, FAN1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation; to: - 5 consanguineous families with homozygous frameshift mutations in FAN1 - FAN1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice - in human retinal pigment epithelium (RPE) cells, FAN1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation |
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| Mendeliome v0.2859 | JARID2 |
Zornitza Stark gene: JARID2 was added gene: JARID2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JARID2 were set to 23294540 Phenotypes for gene: JARID2 were set to Intellectual disability Review for gene: JARID2 was set to AMBER Added comment: Emerging evidence that haploinsufficiency causes neurodevelopmental phenotypes, mostly based on CNV data to date. Sources: Expert Review |
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| Mendeliome v0.2853 | TRIP12 | Zornitza Stark commented on gene: TRIP12: At least 10 unrelated patients reported with ID with or without autism (PMIDs: 27848077, 28251352). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2847 | CLCC1 |
Bryony Thompson gene: CLCC1 was added gene: CLCC1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CLCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLCC1 were set to 30157172 Phenotypes for gene: CLCC1 were set to Retinitis pigmentosa 32 Review for gene: CLCC1 was set to AMBER Added comment: A presumptive Pakastani founder mutation (c.75C>A, p.D25E) was identified in 8 consanguineous arRP families. A knockout zebrafish model and a Clcc1 +/- mouse model had a supporting retinal phenotype. Sources: Expert list |
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| Mendeliome v0.2842 | B9D1 |
Zornitza Stark changed review comment from: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype. Sources: Expert list; to: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. This latter individual had a splice site variant and a deletion. Splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant i dont see the results are usable PMID: 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant. |
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| Mendeliome v0.2839 | BBIP1 | Zornitza Stark edited their review of gene: BBIP1: Added comment: Additional family reported.; Changed publications: 24026985, 32055034 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2832 | STARD7 |
Zornitza Stark gene: STARD7 was added gene: STARD7 was added to Mendeliome. Sources: Expert list STR tags were added to gene: STARD7. Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: STARD7 were set to 11701600; 24114805; 31664034 Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876 Mode of pathogenicity for gene: STARD7 was set to Other Review for gene: STARD7 was set to GREEN Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene. Sources: Expert list |
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| Mendeliome v0.2825 | PDXK |
Russell Gear gene: PDXK was added gene: PDXK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDXK were set to (PMID: 31187503) Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy Review for gene: PDXK was set to RED Added comment: Currently two unrelated families with axonal polyneuropathy and optic atrophy described in the same paper, with bi-allelic PDXK pathogenic variants. Functional work in the same paper includes work on patient derived fibroblasts, measurement of an axonal damage biomarker (NFL protein), and response to PLP supplementation treatment. Need one further unrelated family to upgrade to green? Sources: Literature |
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| Mendeliome v0.2814 | LRRC56 |
Elena Savva gene: LRRC56 was added gene: LRRC56 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC56 were set to PMID: 30388400 Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254 Added comment: PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient. 3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus Sources: Expert list |
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| Mendeliome v0.2806 | GFI1B |
Bryony Thompson gene: GFI1B was added gene: GFI1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872 Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900 Review for gene: GFI1B was set to GREEN Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development. Sources: Literature |
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| Mendeliome v0.2791 | CEP112 |
Bryony Thompson gene: CEP112 was added gene: CEP112 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP112 were set to 31654588 Phenotypes for gene: CEP112 were set to Acephalic spermatozoa; infertility Review for gene: CEP112 was set to AMBER Added comment: Two unrelated cases reported with acephalic spermatozoa, one case with a homozygous nonsense variant and the other case with biallelic missense variants. CEP112 expression was significantly reduced in one of the cases, suggesting loss of function as a mechanism of disease. Sources: Literature |
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| Mendeliome v0.2790 | PRKD1 | Kristin Rigbye changed review comment from: Only 3 pathogenic missense reported to date, although two of these are recurring in unrelated individuals (ClinVar, Decipher, PMID: 27479907). No functional studies performed.; to: Only 3 pathogenic missense reported to date in unrelated individuals (ClinVar, Decipher, PMID: 27479907). No functional studies performed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2790 | KPNA7 |
Alison Yeung gene: KPNA7 was added gene: KPNA7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KPNA7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KPNA7 were set to 24045845; 32179771 Phenotypes for gene: KPNA7 were set to Epilepsy; intellectual disability Review for gene: KPNA7 was set to RED Added comment: Single family with two siblings Sources: Literature |
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| Mendeliome v0.2788 | NR4A2 |
Zornitza Stark gene: NR4A2 was added gene: NR4A2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NR4A2 were set to 31428396; 30504930; 29770430; 12756136; 9092472 Phenotypes for gene: NR4A2 were set to Intellectual disability; epilepsy Review for gene: NR4A2 was set to GREEN Added comment: Over ten individuals reported with mono-allelic variants in this gene and neurodevelopmental phenotypes. Link with dementia/Parkinson's disease disputed. Sources: Literature |
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| Mendeliome v0.2787 | TET2 | Zornitza Stark edited their review of gene: TET2: Added comment: Association study (PMID 32330418) found enrichment of non-coding and LoF TET2 variants in cohort of individuals with early onset dementia, unclear if this is monogenic or polygenic contribution.; Changed publications: 30890702, 31827242, 32330418 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2786 | TOMM70 |
Zornitza Stark gene: TOMM70 was added gene: TOMM70 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TOMM70 were set to 31907385; 32356556 Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis, developmental delay; White matter abnormalities, developmental delay, regression, movement disorder Review for gene: TOMM70 was set to AMBER Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria. Bi-allelic disease: one individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments. Monoallelic disease: de novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data. Sources: Expert list |
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| Mendeliome v0.2771 | KLB |
Zornitza Stark gene: KLB was added gene: KLB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLB were set to 28754744 Review for gene: KLB was set to GREEN Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Functional analysis showed decreased activity in response to FGF21 and FGF8. KLB is an obligate coreceptor for FGF21 alongside FGFR1. Sources: Literature |
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| Mendeliome v0.2769 | NDNF |
Zornitza Stark gene: NDNF was added gene: NDNF was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NDNF were set to 31883645 Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH) Review for gene: NDNF was set to GREEN Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models. Sources: Literature |
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| Mendeliome v0.2767 | UGDH |
Zornitza Stark gene: UGDH was added gene: UGDH was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGDH were set to 32001716 Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792 Review for gene: UGDH was set to GREEN Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode. UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate). Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors Sources: Literature |
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| Mendeliome v0.2764 | YIF1B |
Zornitza Stark gene: YIF1B was added gene: YIF1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to 32006098; 26077767 Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement Review for gene: YIF1B was set to GREEN Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. Sources: Literature |
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| Mendeliome v0.2759 | TNRC6B | Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2758 | CDC42BPB |
Zornitza Stark gene: CDC42BPB was added gene: CDC42BPB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDC42BPB were set to 32031333 Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality Review for gene: CDC42BPB was set to GREEN Added comment: 14 individuals with missense and loss-of-function CDC42BPB variants reported. Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc. Most variants occurred as de novo events (11/14) while inheritance was not available for few (3/14). Sources: Literature |
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| Mendeliome v0.2743 | CFAP43 | Zornitza Stark Added comment: Comment when marking as ready: Good evidence for bi-allelic disease, much less so for mono-allelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2742 | CFAP43 |
Elena Savva gene: CFAP43 was added gene: CFAP43 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP43 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551 Phenotypes for gene: CFAP43 were set to Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592 Added comment: aka WDR96 PMID: 31884020 - animal models (mouse, frog) demonstrate the protein localizes in ciliary axoneme and is involved in MOTILE cilia movement. LOF CFAP43 caused mucus acucmulation in airways, impaired spermatogenesis and hydrocephalus. PMID: 28552195 - 3x chet (bilallelic PTCs or chet PTC/missense) with abnormal sperm motility. Null mouse models were also infertile. PMID: 31004071 - one family with a heterozygous nonsense and AD inheritance of late onset hydrocephaly (checked in Mutalyzer, variant is NMD predicted). Abnormal cilia observed from mucosa sample. Null mice also show abnormal sperm and dilation of brain ventricles. PMID: 29449551 - reports an additional 10 patients with either homozygous PTCs or chet PTC/missense who were infertile with flagella defects Summary: single report of AD hydrocephaly Sources: Literature |
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| Mendeliome v0.2729 | CCDC28B | Zornitza Stark edited their review of gene: CCDC28B: Added comment: PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.; Changed rating: AMBER; Changed publications: 32139166; Changed phenotypes: {Bardet-Biedl syndrome 1, modifier of}, MIM#209900, Joubert syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2729 | C21orf59 | Zornitza Stark Added comment: Comment when marking as ready: p.Tyr245* recurrent in the Ashkenazi Jewish population | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2723 | ARMC9 | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2723 | ARMC9 | Zornitza Stark edited their review of gene: ARMC9: Added comment: ARMC9 localizes to the ciliary basal body and daughter centriole and is predicted to function in ciliogenesis PMID: 28625504 - 8 families with Joubert syndrome, all variant types detected. Functional studies show protein localizes at the basal body and upregulates during ciliogenesis. Zebrafish with frameshift mutation recapitulated the human phenotype including a curved body, coloboma, retinal dystrophy and less cilia.; Changed rating: GREEN; Changed publications: 28625504 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2693 | ATP5A1 | Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name: ATP5F1A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2681 | MAN2B2 |
Zornitza Stark gene: MAN2B2 was added gene: MAN2B2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAN2B2 were set to 31775018 Phenotypes for gene: MAN2B2 were set to Congenital disorder of glycosylation; immunodeficiency Review for gene: MAN2B2 was set to RED Added comment: Single individual reported. Sources: Literature |
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| Mendeliome v0.2676 | PIK3CG |
Zornitza Stark gene: PIK3CG was added gene: PIK3CG was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PIK3CG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3CG were set to 32001535; 31554793 Phenotypes for gene: PIK3CG were set to Immune dysregulation; HLH-like; childhood-onset antibody defects; cytopenias; T lymphocytic pneumonitis and colitis Review for gene: PIK3CG was set to GREEN Added comment: Two individuals with complex immunological phenotypes reported and a mouse model. Sources: Literature |
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| Mendeliome v0.2674 | RC3H1 |
Zornitza Stark changed review comment from: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data. Sources: Literature; to: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data including mouse model. Sources: Literature |
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| Mendeliome v0.2674 | RC3H1 |
Zornitza Stark gene: RC3H1 was added gene: RC3H1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RC3H1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RC3H1 were set to 31636267 Phenotypes for gene: RC3H1 were set to Relapsing HLH Review for gene: RC3H1 was set to RED Added comment: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data. Sources: Literature |
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| Mendeliome v0.2669 | ITPKB |
Zornitza Stark gene: ITPKB was added gene: ITPKB was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITPKB were set to 31987846 Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells Review for gene: ITPKB was set to RED Added comment: Single individual with homozygous bi-allelic LoF variant reported. Sources: Literature |
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| Mendeliome v0.2668 | PSMB10 |
Zornitza Stark gene: PSMB10 was added gene: PSMB10 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMB10 were set to 31783057 Phenotypes for gene: PSMB10 were set to Autoinflammatory syndrome Review for gene: PSMB10 was set to RED Added comment: PSMB10 is part of the immunoproteasome, and other components cause auto inflammatory disorders. Single individual with homozygous missense variant reported. Sources: Literature |
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| Mendeliome v0.2659 | SNORA31 |
Zornitza Stark gene: SNORA31 was added gene: SNORA31 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SNORA31 were set to 31806906 Phenotypes for gene: SNORA31 were set to Susceptibility to HSV1 encephalitis Review for gene: SNORA31 was set to GREEN Added comment: Five unrelated individuals reported with rare missense variants in this gene, functional data to support susceptibility to herpes simplex encephalitis. Sources: Expert list |
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| Mendeliome v0.2649 | ATAD3A |
Zornitza Stark edited their review of gene: ATAD3A: Added comment: Mode of pathogenicity includes: i) bi-allelic missense and nonsense variants and bi-allelic deletions that create an ATAD3B/ATAD3A fusion gene under the lowly expressed ATAD3B promoter ii) monoallelic dominant-negative missense variants (either de novo or inherited) and de novo monoallelic duplications creating a dominant negative ATAD3A/ATAD3C fusion gene; Changed publications: 27640307, 32004445, 28549128; Changed phenotypes: Harel-Yoon syndrome, MIM# 617183, Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810 |
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| Mendeliome v0.2646 | CTSA | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2646 | CTSA | Zornitza Stark commented on gene: CTSA: Mono-allelic variants cause arteriopathy with strokes and leukodystrophy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2641 | CDK5 | Zornitza Stark changed review comment from: Single consanguineous family with multiple affected individuals reported.; to: Single consanguineous family with multiple affected individuals reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2636 | VPS51 |
Zornitza Stark gene: VPS51 was added gene: VPS51 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS51 were set to 30624672; 31207318 Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606 Review for gene: VPS51 was set to AMBER Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable. Sources: Expert list |
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| Mendeliome v0.2635 | CTSA | Zornitza Stark changed review comment from: Bi-allelic variants cause galactosialidosis, and mono-allelic variants cause CARASAL.; to: Bi-allelic variants associated with galactosialidosis, and mono-allelic variants associated with CARASAL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2634 | CDK19 |
Zornitza Stark gene: CDK19 was added gene: CDK19 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDK19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDK19 were set to 32330417 Phenotypes for gene: CDK19 were set to Intellectual disability; epileptic encephalopathy Review for gene: CDK19 was set to GREEN Added comment: Three unrelated individuals with de novo missense variants reported, and intellectual disability/epileptic encephalopathy. Supportive functional data. Sources: Literature |
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| Mendeliome v0.2632 | MNS1 |
Zornitza Stark gene: MNS1 was added gene: MNS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MNS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MNS1 were set to 31534215; 30148830 Phenotypes for gene: MNS1 were set to Heterotaxy; male infertility Review for gene: MNS1 was set to GREEN Added comment: Eight families reported altogether, three LoF variants. Four Amish families share same homozygous founder variant, and some of the other reported families are consanguineous and share another founder variant. A reported female with a third variant, also had a homozygous variant in DNAH5 with a blended phenotype postulated. Sources: Literature |
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| Mendeliome v0.2630 | DHX37 |
Zornitza Stark gene: DHX37 was added gene: DHX37 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHX37 were set to 31337883; 31745530 Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS) Review for gene: DHX37 was set to GREEN Added comment: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies. Sources: Literature |
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| Mendeliome v0.2626 | RAMP2 |
Zornitza Stark gene: RAMP2 was added gene: RAMP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAMP2 were set to 31000793 Phenotypes for gene: RAMP2 were set to Primary open angle glaucoma Review for gene: RAMP2 was set to AMBER Added comment: Six variants identified in 16 of 4763 POAG patients from large cohorts; none identified in 10,953 control individuals. Some functional data. Sources: Literature |
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| Mendeliome v0.2625 | ALPK1 |
Zornitza Stark changed review comment from: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling. Sources: Literature; to: Three unrelated families reported with PFAPA phenotype. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling. Sources: Literature |
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| Mendeliome v0.2625 | ALPK1 | Zornitza Stark edited their review of gene: ALPK1: Added comment: Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met) and ROSAH syndrome phenotype. Pancytopaenia and recurrent infections present in some.; Changed rating: GREEN; Changed publications: 31053777, 30967659, 31939038; Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, ROSAH syndrome, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2624 | MEPE |
Zornitza Stark gene: MEPE was added gene: MEPE was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MEPE were set to 30287925 Phenotypes for gene: MEPE were set to hereditary congenital facial paresis; otosclerosis Review for gene: MEPE was set to AMBER Added comment: Single four-generation family reported with variant in this gene segregating nonprogressive HCFP and mixed hearing loss (HL). Damaging variants (truncating/frameshift) found to be enriched in otosclerosis cohort (p = 0.0006–0.0060). Sources: Literature |
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| Mendeliome v0.2623 | PAICS |
Zornitza Stark gene: PAICS was added gene: PAICS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PAICS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAICS were set to 31600779 Phenotypes for gene: PAICS were set to Polyhydramnios; multiple congenital abnormalities Review for gene: PAICS was set to RED Added comment: Two sibs from single family reported with homozygous missense variant. Functional data to demonstrate effect on protein function. Sources: Literature |
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| Mendeliome v0.2621 | POLR3GL | Zornitza Stark Added comment: Comment when marking as ready: Three cases altogether but the phenotypes are very different -- may still represent a spectrum with the more severe phenotypes resulting from truncating variants but further cases needed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2620 | GALM |
Hazel Phillimore gene: GALM was added gene: GALM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to PMID: 30451973; 30910422 Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia Review for gene: GALM was set to GREEN Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422) Sources: Literature |
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| Mendeliome v0.2620 | POLR3GL |
Paul De Fazio gene: POLR3GL was added gene: POLR3GL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POLR3GL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3GL were set to 31089205; 31695177 Phenotypes for gene: POLR3GL were set to endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy Review for gene: POLR3GL was set to AMBER gene: POLR3GL was marked as current diagnostic Added comment: Biallelic canonical splice variants were identified in monozygotic twins and another individual with similar phenotypes from 2 unrelated families. Variants were inherited from carrier parents. RNA studies confirmed exon skipping occurs in all affected individuals. A separate study identified a homozygous nonsense variant in an individual with features of Neonatal progeroid syndrome/Wiedemann–Rautenstrauch syndrome. Quantitative PCR showed reduction in mRNA suggestive of NMD. Sources: Literature |
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| Mendeliome v0.2620 | TSPEAR | Zornitza Stark Added comment: Comment when marking as ready: Association with isolated deafness is DISPUTED. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2613 | TBL1Y | Zornitza Stark Added comment: Comment when marking as ready: Single family, some functional data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2611 | TSPEAR | Chern Lim changed review comment from: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families. Functional study supported LoF. (PMIDs: 27736875, 30046887); to: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families in 2 papers. Functional study supported LoF. (PMIDs: 27736875, 30046887) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2611 | PDGFRB |
Ee Ming Wong changed review comment from: - > 3 unrelated families - Functional studies on patient fibroblasts, HeLa and HEK293 cells harbouring mutant constructs demonstrate constitutive tyrosine kinase activation (gain of function) compared with WT constructs; to: - > 3 unrelated individuals diagnosed with Penttinen syndrome - Functional studies on patient fibroblasts, HeLa and HEK293 cells harbouring mutant constructs demonstrate constitutive tyrosine kinase activation (gain of function) compared with WT constructs |
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| Mendeliome v0.2611 | TBL1Y |
Paul De Fazio changed review comment from: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate. Sources: Literature; to: Y-linked inheritance pattern. Complete segregation of a missense variant demonstrated in 9 affected males in a 5-generation pedigree. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate. Sources: Literature |
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| Mendeliome v0.2611 | TBL1Y |
Paul De Fazio changed review comment from: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate. Sources: Literature; to: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate. Sources: Literature |
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| Mendeliome v0.2611 | TBL1Y |
Paul De Fazio gene: TBL1Y was added gene: TBL1Y was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TBL1Y was set to Other Publications for gene: TBL1Y were set to 30341416 Phenotypes for gene: TBL1Y were set to Hearing loss Review for gene: TBL1Y was set to RED gene: TBL1Y was marked as current diagnostic Added comment: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate. Sources: Literature |
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| Mendeliome v0.2611 | FOXF2 | Zornitza Stark Added comment: Comment when marking as ready: Single family: variant has functional data to demonstrate effect on protein, plus mouse model supports gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2610 | DGCR8 |
Chern Lim gene: DGCR8 was added gene: DGCR8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DGCR8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DGCR8 were set to 31805011 Phenotypes for gene: DGCR8 were set to Early-onset multinodular goiter and schwannomatosis Review for gene: DGCR8 was set to RED Added comment: A germline missense variant segregates in one family with autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter (MNG) with schwannomatosis. The missense is also a recurrent somatic missense variant in Wilms tumour. (PMID:31805011) Sources: Literature |
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| Mendeliome v0.2607 | FOXF2 |
Hazel Phillimore changed review comment from: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639). This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403). Sources: Literature; to: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639). This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403). Previous names for FOXF2 include FKHL6 and FREAC2. Sources: Literature |
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| Mendeliome v0.2607 | FOXF2 |
Hazel Phillimore gene: FOXF2 was added gene: FOXF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FOXF2 were set to PMID: 30561639; 22022403 Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea Review for gene: FOXF2 was set to AMBER Added comment: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639). This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403). Sources: Literature |
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| Mendeliome v0.2602 | CACNB4 | Zornitza Stark changed review comment from: One multigenerational family and supportive animal model data.; to: One multigenerational family with ataxia and supportive animal model data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2602 | CACNB4 | Zornitza Stark edited their review of gene: CACNB4: Added comment: PMID 32176688: A homozygous missense variant (Leu126Pro) reported in two siblings with intellectual disability, psychomotor retardation, blindness, epilepsy, movement disorder and cerebellar atrophy. Some functional data.; Changed publications: 10762541, 9628818, 27003325, 32176688; Changed phenotypes: Episodic ataxia, type 5, MIM#613855, Intellectual disability, Epilepsy, Movement disorder | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2598 | WDR83OS |
Ee Ming Wong gene: WDR83OS was added gene: WDR83OS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WDR83OS were set to PMID: 30250217 Phenotypes for gene: WDR83OS were set to Cholestasis Review for gene: WDR83OS was set to RED Added comment: - 1 consanguineous family with 3 affected individuals found to carry a homozygous splice site variant in WDR83OS - The variant results in an aberrant truncated RNA transcript as demonstrated by RT-PCR Sources: Literature |
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| Mendeliome v0.2592 | LSR |
Ee Ming Wong gene: LSR was added gene: LSR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LSR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSR were set to PMID: 30250217 Phenotypes for gene: LSR were set to transient neonatal cholestasis; intellectual disability; short stature Review for gene: LSR was set to RED Added comment: 1 individual from 1 consanguineous family carrying a homozygous missense variant in LSR Sources: Literature |
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| Mendeliome v0.2591 | USP53 |
Ee Ming Wong gene: USP53 was added gene: USP53 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: USP53 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP53 were set to PMID: 30250217 Phenotypes for gene: USP53 were set to Deafness Review for gene: USP53 was set to RED Added comment: 1 consanguineous family carrying a homozygous truncating variant in USP53 Sources: Literature |
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| Mendeliome v0.2591 | PPM1F |
Ee Ming Wong gene: PPM1F was added gene: PPM1F was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPM1F was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPM1F were set to PMID: 30250217 Phenotypes for gene: PPM1F were set to sclerosing cholangitis; short stature; hypothyroidism; abnormal tongue pigmentation Review for gene: PPM1F was set to RED Added comment: 1 consanguineous family found to carry a homozygous missense variant in PPM1F Sources: Literature |
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| Mendeliome v0.2588 | KLC2 |
Zornitza Stark gene: KLC2 was added gene: KLC2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KLC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KLC2 were set to 26385635 Phenotypes for gene: KLC2 were set to Spastic paraplegia, optic atrophy, and neuropathy MIM#609541 Review for gene: KLC2 was set to GREEN Added comment: In 73 Brazilian patients and 2 sibs of Egyptian descent with SPOAN, a homozygous 216-bp deletion in the noncoding upstream region of the KLC2 gene was identified. Only reported cause of condition is the upstream large deletion, which is not detected by whole-exome sequencing. Sources: Expert Review |
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| Mendeliome v0.2583 | ALPK1 |
Zornitza Stark gene: ALPK1 was added gene: ALPK1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALPK1 were set to 31053777 Phenotypes for gene: ALPK1 were set to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome Review for gene: ALPK1 was set to AMBER Added comment: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling. Sources: Literature |
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| Mendeliome v0.2581 | LRRC32 |
Zornitza Stark gene: LRRC32 was added gene: LRRC32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC32 were set to 30976112 Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy Review for gene: LRRC32 was set to AMBER Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death. Sources: Literature |
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| Mendeliome v0.2580 | KIF12 |
Ee Ming Wong gene: KIF12 was added gene: KIF12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF12 were set to PMID: 30250217; 30976738 Phenotypes for gene: KIF12 were set to Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT) Review for gene: KIF12 was set to AMBER gene: KIF12 was marked as current diagnostic Added comment: > 3 unrelated families,but they are all consanguineous families Sources: Literature |
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| Mendeliome v0.2577 | RHOA | Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2575 | RHOA | Zornitza Stark reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31821646; Phenotypes: hypopigmented areas of the skin, dental anomalies, body asymmetry, limb length discrepancy, MRI abnormalities; Mode of inheritance: Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2574 | IQCE |
Zornitza Stark gene: IQCE was added gene: IQCE was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IQCE were set to 31549751; 28488682 Phenotypes for gene: IQCE were set to Postaxial polydactyly Review for gene: IQCE was set to GREEN Added comment: Four families reported with bi-allelic variants in this gene. The c.895_904del (p.Val301Serfs*8) was found in three of the families without sharing a common haplotype, suggesting a recurrent mechanism. RNA expression analysis on patients’ fibroblasts showed that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrated a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects. Sources: Literature |
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| Mendeliome v0.2573 | NKX2-3 |
Zornitza Stark gene: NKX2-3 was added gene: NKX2-3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NKX2-3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NKX2-3 were set to 31498527 Phenotypes for gene: NKX2-3 were set to Intestinal varicosities Review for gene: NKX2-3 was set to RED Added comment: Single multiplex family where truncating variant in this gene segregated with intestinal varicosities with a LOD score of 3.3. NKX2‐3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice. Sources: Literature |
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| Mendeliome v0.2572 | RPSA | Zornitza Stark changed review comment from: Four families reported with mono allelic variants and idiopathic intestinal varies.; to: Four families reported with mono allelic variants and idiopathic intestinal varies, often in combination with asplenia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2566 | CRAT |
Zornitza Stark gene: CRAT was added gene: CRAT was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CRAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CRAT were set to 29395073; 31448845 Phenotypes for gene: CRAT were set to Neurodegeneration with brain iron accumulation 8, MIM# 617917; Leigh syndrome Review for gene: CRAT was set to AMBER Added comment: Two unrelated families reported with bi-allelic variants, one with NBIA and one with Leigh syndrome phenotype. Sources: Literature |
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| Mendeliome v0.2561 | B4GAT1 | Zornitza Stark changed review comment from: Two families reported.; to: Two families reported and two animal models. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2556 | THG1L |
Zornitza Stark changed review comment from: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA. Sources: Literature; to: Four Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA. A carrier rate of 0.8%, but no THG1L V55A homozygotes, was found in a cohort of 3,232 unrelated Ashkenazi Jewish individuals, and no homozygotes found in Exac or gnomAD. Sources: Literature |
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| Mendeliome v0.2554 | THG1L |
Zornitza Stark gene: THG1L was added gene: THG1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: THG1L were set to 27307223; 31168944; 30214071 Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800 Review for gene: THG1L was set to AMBER Added comment: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA. Sources: Literature |
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| Mendeliome v0.2553 | TRPV1 |
Zornitza Stark gene: TRPV1 was added gene: TRPV1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRPV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPV1 were set to 29930394 Phenotypes for gene: TRPV1 were set to Susceptibility to malignant hyperthermia Review for gene: TRPV1 was set to RED Added comment: Two individuals reported with rare/novel missense variants in this gene, some functional data. Sources: Literature |
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| Mendeliome v0.2551 | ZP2 |
Zornitza Stark gene: ZP2 was added gene: ZP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZP2 were set to 30810869; 29895852 Phenotypes for gene: ZP2 were set to Female infertility Review for gene: ZP2 was set to GREEN Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and thin zona pellucida. Sources: Literature |
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| Mendeliome v0.2550 | RSRC1 | Zornitza Stark edited their review of gene: RSRC1: Added comment: 17 additional individuals reported.; Changed rating: GREEN; Changed publications: 28640246, 29522154, 32227164; Changed phenotypes: Intellectual developmental disorder, autosomal recessive 70, MIM# 618402 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2549 | GAD1 | Zornitza Stark changed review comment from: Single family reported with bi-allelic variants. Association studies linking with neuropsychiatric issues.; to: Single family reported with bi-allelic variants and CP phenotype. Association studies linking with neuropsychiatric issues. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2549 | GAD1 | Zornitza Stark edited their review of gene: GAD1: Added comment: 2020: 11 individuals from 6 consanguineous families reported with bi-allelic LOF variant and a developmental/epileptic encephalopathy. Seizure onset occurred in the first 2 months of life in all. All 10 individuals, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight individuals had joint contractures and/or pes equinovarus. Seven presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1−/− mouse model. Four individuals died before 4 years of age.; Changed rating: GREEN; Changed publications: 15571623, 32282878; Changed phenotypes: Cerebral palsy, spastic quadriplegic, 1, MIM#603513, Developmental and epileptic encephalopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2548 | GALNT2 |
Zornitza Stark gene: GALNT2 was added gene: GALNT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALNT2 were set to 32293671 Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation Review for gene: GALNT2 was set to GREEN Added comment: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. Sources: Literature |
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| Mendeliome v0.2547 | C7orf43 | Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name: MAP11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2546 | C7orf43 |
Zornitza Stark gene: C7orf43 was added gene: C7orf43 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C7orf43 were set to 30715179 Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351 Review for gene: C7orf43 was set to AMBER Added comment: Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model. Sources: Literature |
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| Mendeliome v0.2539 | TSEN34 | Zornitza Stark Added comment: Comment when marking as ready: Reviewed ClinVar: all variants submitted are VOUS or LB, except for one LP, but no further details provided. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2532 | TSEN54 | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2526 | NDE1 | Zornitza Stark Added comment: Comment when marking as ready: The two OMIM phenotypes likely represent a spectrum of brain abnormalities associated with this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2496 | POLR1B | Zornitza Stark changed review comment from: Five unrelated families and a zebrafish model.; to: Five unrelated families and a zebrafish model. Note four of the families had missense variants affecting same residue, p.Arg1003 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2496 | POLR1B | Zornitza Stark changed review comment from: Six unrelated families and a zebrafish model.; to: Five unrelated families and a zebrafish model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2493 | C1orf194 | Zornitza Stark Added comment: Comment when marking as ready: Two unrelated families with missense variants, one with intermediate CMT, the other with demyelinating CMT. Different phenotypic manifestations may relate to different mechanism, but this remains to be fully elucidated. Supportive mouse model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2470 | ABCC1 |
Zornitza Stark gene: ABCC1 was added gene: ABCC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ABCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ABCC1 were set to 31273342 Phenotypes for gene: ABCC1 were set to Nonsyndromic hearing loss Review for gene: ABCC1 was set to AMBER Added comment: Total of 3 variants reported in 3 families, including 1 which segregates in a large family (10 affected) PMID: 31273342; Li 2019: Reported 3 different het missense in 3 families with postlingual ADNSHL. 1 missense segregated in a large Chinese family. This variant is present in gnomAD (10 hets), but onset noted to be in 2nd or 3rd decade of life. Functional studies performed. Other 2 variants reported absent in gnomAD. Amber rating in light of gnomad frequency of one of the reported variants. Sources: Literature |
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| Mendeliome v0.2455 | FEM1B | Zornitza Stark Added comment: Comment when marking as ready: Agree cannot be confident these represent three unrelated families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2450 | SLC44A1 | Zornitza Stark Added comment: Comment when marking as ready: Childhood onset neurodegeneration | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2449 | SMCHD1 | Zornitza Stark Added comment: Comment when marking as ready: Note association with FSHD2 is postulated to have digenic inheritance, caused by the combination of a heterozygous mutation in the SMCHD1 gene (614982) on chromosome 18p and presence of a haplotype on chromosome 4 that is permissive for DUX4 (606009) expression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | SLC6A6 |
Chern Lim gene: SLC6A6 was added gene: SLC6A6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034 Phenotypes for gene: SLC6A6 were set to Early retinal degeneration; cardiomyopathy Review for gene: SLC6A6 was set to AMBER Added comment: Different homozygous missense variants in 2 unrelated consanguineous families with early retinal degeneration, some functional studies. Patients in one of the families also had cardiomyopathy. (PMIDs: 31345061, 31903486) One dilated cardiomyopathy patient with a homozygous deletion at a splice site (PMID: 29886034). Sources: Literature |
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| Mendeliome v0.2440 | TMPRSS9 |
Chern Lim gene: TMPRSS9 was added gene: TMPRSS9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMPRSS9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMPRSS9 were set to 31943016 Phenotypes for gene: TMPRSS9 were set to autism spectrum disorder Review for gene: TMPRSS9 was set to RED Added comment: Association with Mendelian disease not established. Is a candidate gene for autism spectrum disorder: single patient, compound heterozygous nonsense variants. Functional studies showed Tmprss9 gene is expressed in mouse brain, knockout mice had decreased social interest and social recognition. (PMID: 31943016) Sources: Literature |
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| Mendeliome v0.2440 | MCAT |
Chern Lim gene: MCAT was added gene: MCAT was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MCAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCAT were set to 31915829 Phenotypes for gene: MCAT were set to progressive autosomal recessive optic neuropathy Review for gene: MCAT was set to RED Added comment: One family reported - a consanguineous family, two homozygous missense variants in both affected siblings. Functional studies showed both missense together have synergic impact on MCAT protein misfolding; p.(L81R) had more impact on MCAT protein expression reduction than did the p.(R212W); some study in conditional knockout mice. (PMID:31915829) Sources: Literature |
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| Mendeliome v0.2440 | CAP2 | Melanie Marty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | CAP2 | Melanie Marty edited their review of gene: CAP2: Added comment: 2 patients with dilated cardiomyopathy from 1 consanguineous family. The splice variant identified in this family was proven to cause exon skipping and functional studies showed protein level was reduced. A Cap2 knockout mouse model correlated with the clinical phenotype of DCM and cardiac conduction disease, but not the other effects on growth, viability, wound healing and eye development.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | WIPI2 | Melanie Marty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | WIPI2 | Melanie Marty edited their review of gene: WIPI2: Added comment: Four homozygous patients from one consanguineous family with intellectual developmental, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function.; Changed rating: RED; Changed phenotypes: Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | ATOH7 | Paul De Fazio changed review comment from: Segregates with disease in 3 consanguineous families from Pakistan/Turkey and one non-consanguineous family of Swiss origin. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation.; to: Segregates with disease in 3 consanguineous families from Pakistan/Turkey with global eye abnormalities, and one non-consanguineous family of Swiss origin with optic nerve hypoplasia. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation (in mice). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | GFAP | Paul De Fazio changed review comment from: Many (>20) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | GFAP | Paul De Fazio changed review comment from: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>20) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | PKDCC |
Paul De Fazio changed review comment from: 2 ("apparently") unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice. Sources: Literature; to: 2 apparently unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice. Sources: Literature |
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| Mendeliome v0.2440 | ORAI1 |
Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias) - Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM) - Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy) |
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| Mendeliome v0.2440 | UBA2 |
Elena Savva gene: UBA2 was added gene: UBA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: UBA2 were set to PMID: 31332306; 31587267 Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly Penetrance for gene: UBA2 were set to unknown Review for gene: UBA2 was set to AMBER Added comment: No OMIM phenotype PMID: 31332306 - a single patient with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in patients with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC. Sources: Literature |
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| Mendeliome v0.2440 | ORAI1 |
Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias) - Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias) - Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy) |
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| Mendeliome v0.2440 | GSX2 | Zornitza Stark Added comment: Comment when marking as ready: Intellectual disability, spastic tetraparesis, dystonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2440 | REC114 |
Michelle Torres gene: REC114 was added gene: REC114 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: REC114 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: REC114 were set to 30388401; 31704776 Phenotypes for gene: REC114 were set to Female infertility Review for gene: REC114 was set to GREEN Added comment: Three variants reported are either within or flanking exon 4. - One hom patient (splice) had a miscarriage, 2 spontaneous complete hydatidiform moles, and 1 complete hydatidiform mole following intrauterine sperm injection (PMID: 30388401) - Two hom unrelated patients from consanguineous families with abnormal pronuclear formation during fertilisation and subsequent early embrionic arrest resulting in female infertility. Both variants (1 missense and 1 splice) were shown to result in LoF (PMID: 31704776) Sources: Literature |
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| Mendeliome v0.2439 | C1orf194 |
Ain Roesley gene: C1orf194 was added gene: C1orf194 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C1orf194 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: C1orf194 were set to PMID: 31199454 Phenotypes for gene: C1orf194 were set to Charcot-Marie-Tooth Review for gene: C1orf194 was set to AMBER Added comment: PMID: 31199454; 2 missense variants in 2 large families segregating in an AD pattern. Mouse models for one of the variants (p.(Ile121Asn) led to impairments in moto and neuromuscular functions Sources: Literature |
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| Mendeliome v0.2439 | POLR1B |
Paul De Fazio changed review comment from: 6 individuals with Treacher-Collins syndrome described: 3 with de novo variants, one inherited from a mosaic father, and two inherited from affected mothers. Knockdown in zebrafish mimics the phenotype. Sources: Literature; to: 6 individuals with Treacher-Collins syndrome described: 3 with de novo variants, one inherited from a mosaic father, and two inherited from affected mothers. Knockdown in zebrafish mimics the phenotype. Sources: Literature |
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| Mendeliome v0.2439 | POLR1B |
Paul De Fazio gene: POLR1B was added gene: POLR1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR1B were set to 31649276 Phenotypes for gene: POLR1B were set to bilateral malar and mandibular hypoplasia; microtia; coloboma; downslanting palpebral fissures; conductive deafness; cleft palate; heart malformations Review for gene: POLR1B was set to AMBER gene: POLR1B was marked as current diagnostic Added comment: 6 individuals with Treacher-Collins syndrome described: 3 with de novo variants, one inherited from a mosaic father, and two inherited from affected mothers. Knockdown in zebrafish mimics the phenotype. Sources: Literature |
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| Mendeliome v0.2436 | WARS |
Naomi Baker gene: WARS was added gene: WARS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783. Phenotypes for gene: WARS were set to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration Review for gene: WARS was set to GREEN Added comment: 14 patients from five families were reported to have WARS-related neuropathy across three publications. Expression studies of mutant demonstrated decreased protein when compared to wild-type. Sources: Literature |
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| Mendeliome v0.2421 | PLOD3 | Alison Yeung Added comment: Comment when marking as ready: >3 unrelated families reported | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2418 | TBX6 |
Alison Yeung Added comment: Comment when marking as ready: Biallelic variants associated with spondylocostal dysostosis in >3 unrelated individuals Mouse model recapitulates phenotype |
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| Mendeliome v0.2416 | FUS | Zornitza Stark commented on gene: FUS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2416 | C9orf72 | Zornitza Stark commented on gene: C9orf72 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2416 | ADAMTS19 |
Alison Yeung Added comment: Comment on list classification: Two different homozygous variants in two consanguineous families. Animal model demonstrates cardiac phenotype Await further reported families |
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| Mendeliome v0.2411 | CAP2 |
Alison Yeung Added comment: Comment on list classification: Currently only one consanguineous family reported. Knockout mouse model shows cardiomyopathy but not other clinical features reported in this family |
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| Mendeliome v0.2401 | CPSF1 |
Kristin Rigbye changed review comment from: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892). Sources: Literature; to: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (PMID: 30689892). Sources: Literature |
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| Mendeliome v0.2401 | CPSF1 |
Kristin Rigbye gene: CPSF1 was added gene: CPSF1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CPSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CPSF1 were set to 30689892 Phenotypes for gene: CPSF1 were set to Myopia 27, 618827; high myopia; early-onset high myopiaHigh myopia Review for gene: CPSF1 was set to GREEN Added comment: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892). Sources: Literature |
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| Mendeliome v0.2395 | SIGMAR1 |
Michelle Torres changed review comment from: PMID: 31511340: - N167I (1 het in gnomAD): in 7 consanguinous families from region of Jordan with a specific type of distal hereditary motor neuropathy of Jerash type (HMNJ). Experiments show loss of function effect. - Lists recent publications with other variants (missense and truncating) in patients with distal hereditary motor neuropathy (dHMN) with mild pyramidal signs and jALS (juvenile ALS); to: PMID: 31511340: - N167I (1 het in gnomAD): in 7 consanguinous families from region of Jordan with a specific type of distal hereditary motor neuropathy of Jerash type (HMNJ). Experiments show loss of function effect. - Lists recent publications with other variants (missense and truncating) in patients with distal hereditary motor neuropathy (dHMN) with mild pyramidal signs and jALS (juvenile ALS) |
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| Mendeliome v0.2392 | GNAI2 |
Elena Savva gene: GNAI2 was added gene: GNAI2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GNAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GNAI2 were set to PMID: 31036916 Phenotypes for gene: GNAI2 were set to Pituitary adenoma, ACTH-secreting, somatic; Ventricular tachycardia, idiopathic 192605; Syndromic developmental disorder Review for gene: GNAI2 was set to AMBER Added comment: Papers associating this gene to tachycardia are very old (pre 2000, OMIM). PMID: 31036916 - a single de novo patient with syndromic developmental disorder Summary: AMBER - one report, may be a coincidental de novo finding Sources: Literature |
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| Mendeliome v0.2386 | FEM1B |
Elena Savva gene: FEM1B was added gene: FEM1B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FEM1B were set to PMID: 31036916 Phenotypes for gene: FEM1B were set to Syndromic global developmental delay Review for gene: FEM1B was set to AMBER Added comment: No OMIM phenotype PMID: 31036916 - a single de novo patient reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. Decipher shows this variant to be in a highly constrained region of the protein. Have selected AMBER for now - not sure if GeneMatcher findings can be used as a 3rd case Sources: Literature |
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| Mendeliome v0.2384 | RXFP2 | Alison Yeung Added comment: Comment on list classification: Only single reported family with animal model reported. Both reviews to date are based on same publication. No new publications/reported cases since this one. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2383 | SMCHD1 |
Teresa Zhao changed review comment from: Seven probands with FSHD reported to have LP/P variants, which all predicted to disrupt the structure and conformation of SMCHD1.; to: Seven probands with FSHD reported to have LP/P variants, which all predicted to disrupt the structure and conformation of SMCHD1. No particular geno-pheno correlation, but location of missense variants within the ATPase domain of MSCHD1 may contribute to the differences in phenotypic outcome (PMID: 31243061) |
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| Mendeliome v0.2383 | GFAP | Paul De Fazio changed review comment from: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2383 | GFAP | Paul De Fazio changed review comment from: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous.; to: Many (>10) de novo individuals described with Alexander disease. Three forms of disease are described with decreasing severity: infant-onset, juveline-onset, and adult-onset. Later-onset cases are more phenotypically heterogeneous. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2378 | WIPI2 |
Melanie Marty gene: WIPI2 was added gene: WIPI2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: WIPI2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WIPI2 were set to 30968111 Phenotypes for gene: WIPI2 were set to Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 Review for gene: WIPI2 was set to AMBER Added comment: Four homozygous patients from one consanguineous family with intellectual developmental, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function. Sources: Literature |
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| Mendeliome v0.2378 | SEC31A |
Hazel Phillimore gene: SEC31A was added gene: SEC31A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEC31A were set to PMID: 30464055 Phenotypes for gene: SEC31A were set to congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive Review for gene: SEC31A was set to AMBER Added comment: Frameshift. c.2776_2777, TA duplication, causing predicted p.A927fs*61 truncation and predicted NMD in 2 affected siblings in consanguineous Bedouin family with severe congenital neurological syndrome with spastic paraplegia, multiple contractures, profound developmental delay and convulsions. Failure to thrive. Lethal by age 4 years. Also had hearing defect, bilateral congenital cataract, horizontal nystagmus, with flat retina and optic atrophy. Supporting functional assays from knockout drosophila. Sources: Literature |
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| Mendeliome v0.2378 | SLC44A1 |
Sebastian Lunke gene: SLC44A1 was added gene: SLC44A1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC44A1 were set to 31855247 Phenotypes for gene: SLC44A1 were set to progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria Review for gene: SLC44A1 was set to GREEN Added comment: Four affected individuals from three families with homozygous frameshift variants. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial. Sources: Literature |
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| Mendeliome v0.2377 | GSX2 |
Elena Savva gene: GSX2 was added gene: GSX2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GSX2 were set to PMID: 31412107 Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646 Review for gene: GSX2 was set to GREEN Added comment: PMID: 31412107 - 2 unrelated patients with homozygous mutations (nonsense, missense). Functional analysis of the missense in transfected HeLa cells demonstrated protein mislocalization and protein expression. Downstream gene expression was also reduced by both mutations. Summary: GREEN - 2 patients and functional evidence Sources: Literature |
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| Mendeliome v0.2376 | PKDCC |
Alison Yeung Added comment: Comment on list classification: Two unrelated consanguineous families reported with different homozygous variants Pre-existing mouse model has similar phenotype Needs more functional evidence or further reported families |
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| Mendeliome v0.2375 | SPEF2 |
Chern Lim gene: SPEF2 was added gene: SPEF2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPEF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPEF2 were set to 31151990; 31278745; 31048344 Phenotypes for gene: SPEF2 were set to Spermatogenic failure 43, MIM#618751 Review for gene: SPEF2 was set to GREEN gene: SPEF2 was marked as current diagnostic Added comment: More than 3 unrelated families reported, all PTVs or splice variant. Functional studies showed SPEF2 protein levels were reduced in patients’ spermatozoa. (PMIDs: 31151990, 31278745, 31048344). Sources: Literature |
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| Mendeliome v0.2372 | ACKR3 |
Elena Savva gene: ACKR3 was added gene: ACKR3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ACKR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACKR3 were set to PMID: 3121183 Phenotypes for gene: ACKR3 were set to Oculomotor synkinesis Review for gene: ACKR3 was set to AMBER Added comment: No phenotype currently listed in OMIM PMID: 3121183 - 1 family (3 siblings and a cousin) with congenital ptosis and oculomotor synkinesis. Mouse model reciprocated the phenotype. Functional assay using transfected HEK293 cells show protein mislocalization and lower binding affinity Emerging gene-disease association Sources: Literature |
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| Mendeliome v0.2365 | ADAMTS19 |
Crystle Lee changed review comment from: PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review; to: Borderline amber/green PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review |
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| Mendeliome v0.2365 | ADAMTS19 |
Crystle Lee changed review comment from: PMID: 31844321; Wünnemann 2020: 4 affected in unrelated 2 consanguineous family with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review; to: PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review |
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| Mendeliome v0.2365 | SAMD12 |
Melanie Marty gene: SAMD12 was added gene: SAMD12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SAMD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SAMD12 were set to 30194086; 29507423 Phenotypes for gene: SAMD12 were set to Epilepsy, familial adult myoclonic, 1 601068 Review for gene: SAMD12 was set to GREEN Added comment: Repeat expansions of intronic TTTCA and TTTTA motifs within SAMD12 have been identified in over 50 Japanese and Chinese families. Most families with affected individuals were heterozygous however 4 patients from 3 families had homozygous repeat expansions, which was associated with a more severe phenotype. Western blot analysis showed decreased levels of the protein in patient brains. Sources: Literature |
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| Mendeliome v0.2365 | FUS |
Elena Savva gene: FUS was added gene: FUS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FUS were set to PMID: 32281455; 20668259; 20385912 Phenotypes for gene: FUS were set to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia 608030; Essential tremor, hereditary, 4 614782 Mode of pathogenicity for gene: FUS was set to Other Review for gene: FUS was set to GREEN Added comment: PMID: 32281455 - Reports a case of Pediatric Amyotrophic Lateral Sclerosis. Reviews and shows multiple other reports of ALS casued by FUS PMID: 20668259 - additional reports of ALS PMID: 20385912 - postulated that disruption of this region may disrupt subcellular distribution of FUS, in turn affecting transcription and RNA processing and conferring a toxic gain of function. Sources: Literature |
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| Mendeliome v0.2365 | ADAMTS19 |
Crystle Lee gene: ADAMTS19 was added gene: ADAMTS19 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ADAMTS19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS19 were set to 31844321 Phenotypes for gene: ADAMTS19 were set to Non-syndromic heart valve disease Review for gene: ADAMTS19 was set to GREEN Added comment: PMID: 31844321; Wünnemann 2020: 4 affected in unrelated 2 consanguineous family with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review |
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| Mendeliome v0.2365 | ELOVL1 | Hazel Phillimore changed review comment from: De novo in 2 unrelated patients. Decrease in ELOVL1 enzyme activity. The same 2 patients are in PMIDs: 30487246 and 29496980 but with different clinical findings. Deafness and optic atrophy are the additional features.; to: De novo missense (S165F) in 2 unrelated patients. Decrease in ELOVL1 enzyme activity. The same 2 patients are in PMIDs: 30487246 and 29496980 but with different clinical findings. Deafness and optic atrophy are the additional features. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2365 | C9orf72 |
Elena Savva gene: C9orf72 was added gene: C9orf72 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: C9orf72 were set to PMID: 30120348; 23284068 Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 Review for gene: C9orf72 was set to AMBER Added comment: Possibly RED Caused by expansion of GGGGCC repeats, dont know if these qualify for mendeliome Sources: Literature |
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| Mendeliome v0.2365 | TNFRSF21 |
Alison Yeung Added comment: Comment on list classification: Report of single family Limited functional evidence: tissue expression studies |
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| Mendeliome v0.2364 | CFAP65 |
Daniel Flanagan gene: CFAP65 was added gene: CFAP65 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CFAP65 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP65 were set to 31501240; 31413122 Phenotypes for gene: CFAP65 were set to Spermatogenic failure 40 618664 Penetrance for gene: CFAP65 were set to unknown Review for gene: CFAP65 was set to GREEN gene: CFAP65 was marked as current diagnostic Added comment: 9 patients with multiple morphological abnormalities of the sperm flagella (MMAF) or completely immotile spermatozoa, in which, homozygous or compound heterozygous truncating CFAP65 variants were identified. Cfap65-mutated male mice displayed typical MMAF phenotypes with severe morphological abnormalities of the sperm flagella (PMID: 31501240, 31413122). Sources: Literature |
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| Mendeliome v0.2364 | CAP2 |
Melanie Marty gene: CAP2 was added gene: CAP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAP2 were set to 30518548 Phenotypes for gene: CAP2 were set to Dilated cardiomyopathy Review for gene: CAP2 was set to AMBER Added comment: 2 patients with dilated cardiomyopathy from 1 consanguineous family. The splice variant identified in this family was proven to cause exon skipping and functional studies showed protein level was reduced. A Cap2 knockout mouse model correlated with the clinical phenotype of DCM and cardiac conduction disease, but not the other effects on growth, viability, wound healing and eye development. Sources: Literature |
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| Mendeliome v0.2364 | USP45 |
Alison Yeung Added comment: Comment on list classification: Two unrelated families Functional studies in animal model recapitulate retinal phenotype |
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| Mendeliome v0.2362 | SYCP2 |
Zornitza Stark gene: SYCP2 was added gene: SYCP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SYCP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SYCP2 were set to 32092049; 31866047 Phenotypes for gene: SYCP2 were set to Male infertility Review for gene: SYCP2 was set to GREEN Added comment: Four individuals and a zebrafish model. Sources: Literature |
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| Mendeliome v0.2361 | MYCN | Ain Roesley changed review comment from: PMID: 30573562; case report of an individual with a missense in MYCN with functional studies done in neuronal progenitor/stem cells demonstrating gain-of-function; to: PMID: 30573562; case report of an individual with a missense in MYCN with functional studies done in neuronal progenitor/stem cells demonstrating gain-of-function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2361 | PKDCC |
Paul De Fazio gene: PKDCC was added gene: PKDCC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PKDCC were set to PMID:30478137; 19097194 Phenotypes for gene: PKDCC were set to Dysmorphism; shortening of extremities Review for gene: PKDCC was set to AMBER gene: PKDCC was marked as current diagnostic Added comment: 2 ("apparently") unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice. Sources: Literature |
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| Mendeliome v0.2361 | MYCN | Ain Roesley edited their review of gene: MYCN: Added comment: PMID: 30573562; case report of an individual with a missense in MYCN with functional studies done in neuronal progenitor/stem cells demonstrating gain-of-function; Changed rating: RED; Changed publications: PMID: 30573562; Changed phenotypes: megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, neuroblastoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2361 | TNFRSF21 |
Shannon Cowie gene: TNFRSF21 was added gene: TNFRSF21 was added to Mendeliome. Sources: Other Mode of inheritance for gene: TNFRSF21 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TNFRSF21 were set to PMID: 31189563 Phenotypes for gene: TNFRSF21 were set to high myopia Review for gene: TNFRSF21 was set to RED gene: TNFRSF21 was marked as current diagnostic Added comment: Source: JMG review Oct 2019 Large Chinese family, including 12 patients with non-syndromic HM Immunofluorescence assay indicated that it is strongly expressed in the mouse eye. Sources: Other |
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| Mendeliome v0.2361 | USP45 |
Kristin Rigbye gene: USP45 was added gene: USP45 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: USP45 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP45 were set to 30573563 Phenotypes for gene: USP45 were set to Leber congenital amaurosis; retinal dystrophy Review for gene: USP45 was set to GREEN Added comment: 2 unrelated Chinese families reported with rare homozygous variants (one missense, one nonsense) and Leber congenital amaurosis. Animal knockout functional studies supported gene-disease association. PMID: 30573563 "By analysing WES data based on allele frequencies of in-house controls, population allele frequencies and in silico prediction tools, two rare homozygous mutations in USP45 were identified in two unrelated families. Immunohistochemistry of USP45 in the human and zebrafish retinal sections revealed enriched expression in the inner segments of photoreceptors. The knockdown of usp45 transcript in zebrafish led to abnormal retinal development with effects on photoreceptors, which could be successfully rescued by wild-type usp45 mRNA. Moreover, targeted knockout of Usp45 in mice caused abnormal electroretinography responses, similar to that seen in patients with LCA." Sources: Literature |
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| Mendeliome v0.2360 | BAZ2B |
Zornitza Stark gene: BAZ2B was added gene: BAZ2B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BAZ2B were set to 31999386; 28135719; 25363768 Phenotypes for gene: BAZ2B were set to Intellectual disability; autism Review for gene: BAZ2B was set to GREEN Added comment: Postulated as a candidate gene for ID/ASD by large-scale studies. Case series reports two individuals with small CNVs and and six with SNVs, mostly LoF type variants. Although the gene is generally intolerant of LoF, some LoF variants present in gnomad ?incomplete penetrance. Additional reported features were inconsistent Sources: Literature |
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| Mendeliome v0.2358 | TPI1 |
Zornitza Stark gene: TPI1 was added gene: TPI1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TPI1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TPI1 were set to Hemolytic anemia due to triosephosphate isomerase deficiency, MIM# 615512 Review for gene: TPI1 was set to GREEN Added comment: Sources: Expert list |
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| Mendeliome v0.2356 | EMG1 |
Zornitza Stark gene: EMG1 was added gene: EMG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: EMG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EMG1 were set to 19463982 Phenotypes for gene: EMG1 were set to Bowen-Conradi syndrome, MIM#211180 Review for gene: EMG1 was set to AMBER Added comment: Founder mutation in Hutterite, D86G. Sources: Expert list |
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| Mendeliome v0.2354 | EIF2AK4 |
Zornitza Stark gene: EIF2AK4 was added gene: EIF2AK4 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: EIF2AK4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EIF2AK4 were set to Pulmonary venoocclusive disease 2, MIM#234810 Review for gene: EIF2AK4 was set to GREEN Added comment: Sources: Expert list |
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| Mendeliome v0.2352 | AGBL5 |
Zornitza Stark gene: AGBL5 was added gene: AGBL5 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AGBL5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGBL5 were set to 26720455; 26355662; 30925032 Phenotypes for gene: AGBL5 were set to Retinitis pigmentosa 75, MIM# 617023 Review for gene: AGBL5 was set to GREEN Added comment: At least three unrelated families reported. Sources: Expert list |
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| Mendeliome v0.2350 | CPT1C |
Bryony Thompson gene: CPT1C was added gene: CPT1C was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CPT1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CPT1C were set to 25751282; 23973755 Phenotypes for gene: CPT1C were set to Spastic paraplegia 73, autosomal dominant MIM#616282 Review for gene: CPT1C was set to GREEN Added comment: Two unrelated families dominant HSP and a supportive mouse model. Sources: Expert list |
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| Mendeliome v0.2348 | ATP2B4 |
Bryony Thompson gene: ATP2B4 was added gene: ATP2B4 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ATP2B4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP2B4 were set to 25119969; 25798335; 29691679 Phenotypes for gene: ATP2B4 were set to Hereditary spastic paraplegia Review for gene: ATP2B4 was set to AMBER Added comment: One Chinese family segregating a missense variant with HSP and one HSP case with a assumed de novo nonsense variant. Supporting in vitro functional assays for the missense variant. Sources: Expert list |
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| Mendeliome v0.2328 | TECTA | Zornitza Stark Added comment: Comment when marking as ready: Both recessive and dominant deafness associations assessed as DEFINITIVE by ClinGen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2320 | SOS1 | Zornitza Stark Added comment: Comment when marking as ready: The association with Noonan syndrome is well established; the association with gingival fibromatosis is questionable. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2318 | SOS1 | Zornitza Stark Mode of pathogenicity for gene: SOS1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2313 | MED13L | Zornitza Stark Added comment: Comment when marking as ready: The evidence for isolated CHD much less compelling than the association with a neurodevelopmental syndrome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2305 | SOS1 | Elena Savva reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 25062969, 17143285, 17143282; Phenotypes: ?Fibromatosis, gingival, 1, 135300, Noonan syndrome 4, 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2304 | XRCC1 |
Bryony Thompson gene: XRCC1 was added gene: XRCC1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: XRCC1 were set to 28002403; 29472272 Phenotypes for gene: XRCC1 were set to Spinocerebellar ataxia, autosomal recessive 26 MIM#617633 Review for gene: XRCC1 was set to GREEN Added comment: Three South Asian cases (one with early adult onset and the other two with onset in childhood) reported with slowly progressive cerebellar ataxia accompanied by sensorimotor neuropathy. All with the recurrent splice variant (c.1293G>C, 2 homozygotes and a compound heterozygote). Mice with conditional deletion of the Xrcc1 gene in the brain showed cerebellar ataxia. Sources: Expert list |
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| Mendeliome v0.2302 | TRPC3 |
Bryony Thompson gene: TRPC3 was added gene: TRPC3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPC3 were set to 25477146; 19351902 Phenotypes for gene: TRPC3 were set to Spinocerebellar ataxia 41 MIM#616410 Mode of pathogenicity for gene: TRPC3 was set to Other Review for gene: TRPC3 was set to AMBER Added comment: A heterozygous gain-of function missense has been identified in a 40-year-old man with adult-onset spinocerebellar ataxia. A mouse model of dominant cerebellar ataxia, termed 'moonwalker', contains a gain-of-function variant in this gene. Sources: Expert list |
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| Mendeliome v0.2300 | SLC9A1 |
Zornitza Stark gene: SLC9A1 was added gene: SLC9A1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC9A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC9A1 were set to 25205112; 30018422; 25760855 Phenotypes for gene: SLC9A1 were set to Lichtenstein-Knorr syndrome, MIM# 616291 Review for gene: SLC9A1 was set to AMBER Added comment: Two families with bi-allelic variants in this gene reported and combination of deafness and ataxia. Sources: Expert list |
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| Mendeliome v0.2298 | MTCL1 |
Bryony Thompson gene: MTCL1 was added gene: MTCL1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MTCL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MTCL1 were set to 30548255; 28283581 Phenotypes for gene: MTCL1 were set to slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia Review for gene: MTCL1 was set to AMBER Added comment: Single case with a homozygous loss of function variant in a Polish study of early-onset cerebellar ataxia, and a single family with a single heterozygous missense (p.Val1435Met) identified in two family members with adult-onset spinocerebellar ataxia. Mtcl1 gene disruption in mice results in abnormal motor coordination with Purkinje cell degeneration Sources: Expert list |
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| Mendeliome v0.2296 | ATG5 |
Bryony Thompson gene: ATG5 was added gene: ATG5 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ATG5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATG5 were set to 16625204; 26812546 Phenotypes for gene: ATG5 were set to Spinocerebellar ataxia, autosomal recessive 25 MIM#617584 Review for gene: ATG5 was set to AMBER Added comment: A homozgyous variant was identified in a single family with two affected siblings. Mice deficient for Atg5 specifically in neural cells and Atg5 null Drosophila develop progressive deficits in motor function. Sources: Expert list |
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| Mendeliome v0.2295 | IL18BP |
Zornitza Stark gene: IL18BP was added gene: IL18BP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL18BP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL18BP were set to 31213488 Phenotypes for gene: IL18BP were set to {?Hepatitis, fulminant viral, susceptibility to} 618549 Review for gene: IL18BP was set to RED Added comment: Single individual reported with homozygous 40bp deletion in this gene and fulminant Hep A hepatitis. Sources: Expert list |
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| Mendeliome v0.2290 | ACOX2 | Zornitza Stark Added comment: Comment when marking as ready: The ACOX2 gene encodes a peroxisomal branched-chain acyl-CoA oxidase involved in bile acid synthesis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.2281 | SIPA1L3 |
Bryony Thompson gene: SIPA1L3 was added gene: SIPA1L3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SIPA1L3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SIPA1L3 were set to 28951961; 27993984; 25804400 Phenotypes for gene: SIPA1L3 were set to Cataract 45 MIM#616851 Review for gene: SIPA1L3 was set to AMBER Added comment: A consanguineous German family segregating a homozygous nonsense mutation in two sisters with congenital cataracts (PMID: 25804400). Null Zebrafish, Xenopus and mouse models recapitulate the human cataract phenotype. A case with congenital cataracts as a feature of their condition harboured a de novo balanced chromosomal translocation, 46,XY,t(2;19)(q37.3;q13.1), where breakpoint mapping and sequencing showed a physical disruption of the 5′UTR of SIPA1L3 (PMID: 26231217). In a case with bilateral congenital cataracts a heterozygous missense (D148Y) was identified and in vitro functional assays of the variant resulted in abnormal actin morphology (PMID: 26231217). Sources: Expert list |
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| Mendeliome v0.2280 | 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 v0.2278 | RNU4ATAC | Zornitza Stark Added comment: Comment when marking as ready: Note gene is not protein coding. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2275 | IFT172 | Zornitza Stark Added comment: Comment when marking as ready: Established ciliopathy gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2259 | MARS2 | Zornitza Stark changed review comment from: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV.; to: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV. Spastic ataxia association: note complex chromosomal rearrangements rather than SNVs reported in group of 54 French Canadians. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.2225 | SHANK2 | Zornitza Stark Added comment: Comment when marking as ready: Reports of CNVs, LoF variants, and missense variants in this gene, generally ascertained in autism cohorts. Some de novo and others inherited from parents with a range of neuropsychiatric phenotypes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2213 | SOX11 |
Zornitza Stark changed review comment from: Heterozygous variant in a patient with Coffin-Siris like syndrome and small kidney; but also rare variants identified in a non-syndromic CAKUT cohort with some functional data. Sources: Expert list; to: Coffin-Siris syndrome: two individuals with de novo mono-allelic missense variants in this gene, mouse model. CAKUT: Heterozygous variant in a patient with Coffin-Siris like syndrome and small kidney; but also rare variants identified in a non-syndromic CAKUT cohort with some functional data. Sources: Expert list |
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| 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 v0.2204 | PET117 |
Zornitza Stark gene: PET117 was added gene: PET117 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PET117 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PET117 were set to 28386624 Phenotypes for gene: PET117 were set to Developmental delay; Regression; Complex IV deficiency Review for gene: PET117 was set to RED Added comment: Two siblings reported, some functional data. PET117 postulated to be a Complex IV assembly factor. Sources: Expert list |
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| Mendeliome v0.2200 | 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 v0.2179 | NME3 |
Zornitza Stark gene: NME3 was added gene: NME3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NME3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NME3 were set to 30587587 Phenotypes for gene: NME3 were set to Hypotonia; Neurodegeneration; Abnormal mitochondrial dynamics Review for gene: NME3 was set to RED Added comment: Single individual reported. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics Sources: Expert list |
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| Mendeliome v0.2178 | MRPS28 |
Zornitza Stark gene: MRPS28 was added gene: MRPS28 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MRPS28 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS28 were set to 30566640 Phenotypes for gene: MRPS28 were set to Intrauterine growth retardation; developmental delay; dysmorphism Review for gene: MRPS28 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.2177 | MRPS25 |
Zornitza Stark gene: MRPS25 was added gene: MRPS25 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MRPS25 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS25 were set to 31039582 Phenotypes for gene: MRPS25 were set to Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum Review for gene: MRPS25 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.2173 | MRPS23 | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2173 | MRPS23 | Zornitza Stark edited their review of gene: MRPS23: Added comment: Four families reported.; Changed rating: GREEN; Changed publications: 26741492, 17873122, 25663021, 28752220; Changed phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies, Cardiomyopathy, Tubulopathy, Lactic acidosis, Structural brain abnormalities | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2173 | MIEF2 |
Zornitza Stark gene: MIEF2 was added gene: MIEF2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MIEF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIEF2 were set to 29361167 Phenotypes for gene: MIEF2 were set to Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency Review for gene: MIEF2 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.2171 | ERAL1 |
Zornitza Stark gene: ERAL1 was added gene: ERAL1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERAL1 were set to 28449065 Phenotypes for gene: ERAL1 were set to Perrault syndrome 6, MIM# 617565 Review for gene: ERAL1 was set to AMBER Added comment: Three individuals from same small geographical location with homozygous missense variant in this gene, functional data. Sources: Expert list |
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| Mendeliome v0.2170 | COX5A |
Zornitza Stark gene: COX5A was added gene: COX5A was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: COX5A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX5A were set to 2824752 Phenotypes for gene: COX5A were set to pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency Review for gene: COX5A was set to RED Added comment: Single family reported. Sources: Expert list |
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| Mendeliome v0.2063 | CFB | Zornitza Stark changed review comment from: Single individual reported, supportive immunophenotyping data.; to: Single individual reported with bi-allelic variants and complement deficiency, supportive immunophenotyping data. Mono-allelic variants linked to susceptibility to aHUS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2050 | CD247 | Zornitza Stark changed review comment from: Also known as CD3Z. Single individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants.; to: Also known as CD3Z. Note one individual reported with homozygous germline nonsense variant, which was present in some T cells, but others had the nonsense variant in combination with one of three different missense somatic variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2050 | CD247 | Zornitza Stark edited their review of gene: CD247: Added comment: Two reports in the literature, note additional two reports in ClinVar; functional data.; Changed rating: GREEN; Changed publications: 16672702, 17170122 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.2005 | MAD2L2 |
Zornitza Stark gene: MAD2L2 was added gene: MAD2L2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MAD2L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAD2L2 were set to 27500492 Phenotypes for gene: MAD2L2 were set to Fanconi anemia, complementation group V, MIM# 617243 Review for gene: MAD2L2 was set to RED Added comment: Single family reported. Sources: Expert list |
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| Mendeliome v0.1999 | HAVCR2 |
Zornitza Stark gene: HAVCR2 was added gene: HAVCR2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HAVCR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HAVCR2 were set to 30374066; 30792187 Phenotypes for gene: HAVCR2 were set to T-cell lymphoma, subcutaneous panniculitis-like, MIM# 618398 Review for gene: HAVCR2 was set to GREEN Added comment: Over 20 unrelated individuals reported, note germline confirmation in only a few. Some variants are recurrent: c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met). Sources: Expert list |
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| Mendeliome v0.1997 | TRIM22 |
Zornitza Stark gene: TRIM22 was added gene: TRIM22 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRIM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRIM22 were set to 26836588 Phenotypes for gene: TRIM22 were set to Inflammatory bowel disease Review for gene: TRIM22 was set to GREEN Added comment: Three unrelated families reported with bi-allelic variants in this gene, and very early onset IBD, some functional data. Sources: Expert list |
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| Mendeliome v0.1995 | ALPI |
Zornitza Stark gene: ALPI was added gene: ALPI was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ALPI was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALPI were set to 29567797 Phenotypes for gene: ALPI were set to Inflammatory bowel disease Review for gene: ALPI was set to AMBER Added comment: Two unrelated individuals, some functional data. Sources: Expert list |
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| Mendeliome v0.1994 | PSMG2 |
Zornitza Stark gene: PSMG2 was added gene: PSMG2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: PSMG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PSMG2 were set to 30664889 Phenotypes for gene: PSMG2 were set to CANDLE syndrome; Chronic atypical neutrophilic dermatitis with lipodystrophy Review for gene: PSMG2 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.1987 | TIRAP | Zornitza Stark changed review comment from: No evidence currently for Mendelian disease association. Some evidence for polymorphisms in this gene influencing susceptibility/protection from infectious disease.; to: No evidence currently for Mendelian disease association. Some evidence for polymorphisms in this gene influencing susceptibility/protection from infectious disease. One family with 8 individuals and bi-allelic variants and susceptibility to staphylococcal disease reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1987 | IRAK1 |
Zornitza Stark gene: IRAK1 was added gene: IRAK1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IRAK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: IRAK1 were set to 28069966 Phenotypes for gene: IRAK1 were set to Susceptibility to bacterial infections Review for gene: IRAK1 was set to RED Added comment: Single individual with MECP2 and IRAK1 deletion, died in infancy, immunological phenotype not fully elucidated. In vitro studies. Sources: Expert list |
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| Mendeliome v0.1985 | DBR1 |
Zornitza Stark gene: DBR1 was added gene: DBR1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DBR1 were set to 29474921 Phenotypes for gene: DBR1 were set to Viral infections of the brainstem Review for gene: DBR1 was set to GREEN Added comment: Seven individuals from three unrelated families with viral brainstem encephalitis and bi-allelic hypomorphic variants. Sources: Expert list |
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| Mendeliome v0.1984 | POLR3F |
Zornitza Stark gene: POLR3F was added gene: POLR3F was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: POLR3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR3F were set to 30211253 Phenotypes for gene: POLR3F were set to Severe VZV infection Review for gene: POLR3F was set to RED Added comment: Missense variant identified in a pair of monozygotic twins. Variant was paternally inherited. Sources: Expert list |
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| Mendeliome v0.1982 | POLR3C |
Zornitza Stark gene: POLR3C was added gene: POLR3C was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: POLR3C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR3C were set to 28783042 Phenotypes for gene: POLR3C were set to Severe VZV infection Review for gene: POLR3C was set to AMBER Added comment: One individual with POLR3C variant and another individual with both POL3RA and POL3RC variants. Sources: Expert list |
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| Mendeliome v0.1974 | IFNAR1 |
Zornitza Stark gene: IFNAR1 was added gene: IFNAR1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IFNAR1 were set to 31270247 Phenotypes for gene: IFNAR1 were set to Severe disease caused by Yellow Fever vaccine and Measles vaccine Review for gene: IFNAR1 was set to AMBER Added comment: Two unrelated individuals reported with bi-allelic LoF variants, some functional data. Sources: Expert list |
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| Mendeliome v0.1972 | IRF9 |
Zornitza Stark gene: IRF9 was added gene: IRF9 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IRF9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IRF9 were set to 30826365; 30143481 Phenotypes for gene: IRF9 were set to Immunodeficiency 65, susceptibility to viral infections 618648 Review for gene: IRF9 was set to AMBER Added comment: Two families reported. Sources: Expert list |
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| Mendeliome v0.1970 | CIB1 |
Zornitza Stark gene: CIB1 was added gene: CIB1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CIB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CIB1 were set to 30068544 Phenotypes for gene: CIB1 were set to Epidermodysplasia verruciformis 3 618267; HPV infections and cancer of the skin Review for gene: CIB1 was set to GREEN Added comment: 24 individuals from 6 families reported. Sources: Expert list |
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| Mendeliome v0.1965 | JAK1 |
Zornitza Stark changed review comment from: Single family reported (mother and two children) with GoF variant. Sources: Expert list; to: Single family reported (mother and two children) with GoF variant and immune dysregulation phenotype. Another individual reported with bi-allelic LoF and susceptibility to mycobacterial infections. Mouse model with NK defect. 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 v0.1959 | IL12RB2 |
Zornitza Stark gene: IL12RB2 was added gene: IL12RB2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL12RB2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL12RB2 were set to 30578351 Phenotypes for gene: IL12RB2 were set to Susceptibility to mycobacteria and Salmonella Review for gene: IL12RB2 was set to RED Added comment: Single individual reported, some functional data. Sources: Expert list |
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| Mendeliome v0.1957 | C17orf62 |
Zornitza Stark gene: C17orf62 was added gene: C17orf62 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C17orf62 were set to 30361506; 30312704; 28351984 Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease Review for gene: C17orf62 was set to GREEN Added comment: Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name) Sources: Expert list |
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| Mendeliome v0.1955 | MKL1 |
Zornitza Stark gene: MKL1 was added gene: MKL1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MKL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MKL1 were set to 32128589; 26224645 Phenotypes for gene: MKL1 were set to Neutropaenia with combined immune deficiency Review for gene: MKL1 was set to AMBER Added comment: Two unrelated families reported. Sources: Expert list |
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| Mendeliome v0.1954 | HYOU1 |
Zornitza Stark gene: HYOU1 was added gene: HYOU1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: HYOU1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HYOU1 were set to 27913302 Phenotypes for gene: HYOU1 were set to Immunodeficiency 59 and hypoglycemia, MIM# 233600 Review for gene: HYOU1 was set to RED Added comment: Single individual reported. Sources: Expert list |
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| Mendeliome v0.1952 | SMARCD2 |
Zornitza Stark gene: SMARCD2 was added gene: SMARCD2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMARCD2 were set to 28369036; 28369034 Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2, MIM# 617475; Neutropaenia; Neurodevelopmental abnormalities in some; Myelodysplasia Review for gene: SMARCD2 was set to GREEN Added comment: Three unrelated families and functional data. Sources: Expert list |
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| Mendeliome v0.1950 | TNFRSF9 |
Zornitza Stark gene: TNFRSF9 was added gene: TNFRSF9 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TNFRSF9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNFRSF9 were set to 30872117; 31501153 Phenotypes for gene: TNFRSF9 were set to EBV lymphoproliferation; B-cell lymphoma; Chronic active EBV infection Review for gene: TNFRSF9 was set to GREEN Added comment: Six unrelated individuals, two with same homozygous G109S missense variant, functional data. Sources: Expert list |
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| Mendeliome v0.1946 | JAK1 |
Zornitza Stark gene: JAK1 was added gene: JAK1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: JAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JAK1 were set to 28111307 Phenotypes for gene: JAK1 were set to Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections Review for gene: JAK1 was set to RED Added comment: Single family reported (mother and two children) with GoF variant. Sources: Expert list |
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| Mendeliome v0.1944 | IL2RB |
Zornitza Stark gene: IL2RB was added gene: IL2RB was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL2RB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL2RB were set to 31040184; 31040185 Phenotypes for gene: IL2RB were set to Immunodeficiency 63 with lymphoproliferation and autoimmunity, MIM# 618495; Lymphoproliferation, lymphadenopathy, hepatosplenomegaly, autoimmune haemolytic anaemia, dermatitis, enteropathy, hypergammaglobulinaemia, recurrent viral (EBV, CMV) infections Review for gene: IL2RB was set to GREEN Added comment: Five families reported. Sources: Expert list |
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| Mendeliome v0.1943 | AP3D1 |
Zornitza Stark gene: AP3D1 was added gene: AP3D1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP3D1 were set to 26744459; 9697856 Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050; Oculocutaneous albinism; Severe neutropaenia; Recurrent infections; Seizures; Hearing loss; Neurodevelopmental delay Review for gene: AP3D1 was set to RED Added comment: Single family and a mouse model. Sources: Expert list |
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| Mendeliome v0.1942 | FAAP24 |
Zornitza Stark gene: FAAP24 was added gene: FAAP24 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FAAP24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAAP24 were set to 27473539 Phenotypes for gene: FAAP24 were set to EBV infection-driven lymphoproliferative disease Review for gene: FAAP24 was set to RED Added comment: Single sib pair with homozygous missense variant, some functional data. Sources: Expert list |
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| Mendeliome v0.1941 | SH3KBP1 |
Zornitza Stark gene: SH3KBP1 was added gene: SH3KBP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SH3KBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SH3KBP1 were set to 29636373; 21708930 Phenotypes for gene: SH3KBP1 were set to Immunodeficiency 61, MIM# 300310 Review for gene: SH3KBP1 was set to RED Added comment: Single family reported, 247.5-kb intragenic deletion detected by array. Sources: Expert list |
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| Mendeliome v0.1940 | ARHGEF1 |
Zornitza Stark gene: ARHGEF1 was added gene: ARHGEF1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARHGEF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARHGEF1 were set to 30521495 Phenotypes for gene: ARHGEF1 were set to Immunodeficiency 62, MIM#618459 Review for gene: ARHGEF1 was set to RED Added comment: Single family, functional data. Sources: Expert list |
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| Mendeliome v0.1936 | IRF2BP2 |
Zornitza Stark gene: IRF2BP2 was added gene: IRF2BP2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IRF2BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IRF2BP2 were set to 27016798 Phenotypes for gene: IRF2BP2 were set to Immunodeficiency, common variable, 14, MIM# 617765 Review for gene: IRF2BP2 was set to RED Added comment: Single family reported only. Sources: Expert list |
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| Mendeliome v0.1933 | 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 v0.1927 | ERBIN |
Zornitza Stark gene: ERBIN was added gene: ERBIN was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ERBIN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ERBIN were set to 28126831 Phenotypes for gene: ERBIN were set to Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some Review for gene: ERBIN was set to AMBER Added comment: Single family and functional data. Sources: Expert list |
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| Mendeliome v0.1925 | ZNF341 |
Zornitza Stark gene: ZNF341 was added gene: ZNF341 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ZNF341 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF341 were set to 29907691; 29907690 Phenotypes for gene: ZNF341 were set to Hyper-IgE recurrent infection syndrome 3, autosomal recessive, MIM# 618282; Mild facial dysmorphism; Early onset eczema; Recurrent bacterial skin infections, abscesses; Recurrent respiratory infections, lung abscesses and pneumothoraces; Hyperextensible joints, bone fractures, retention of primary teeth Review for gene: ZNF341 was set to GREEN Added comment: 19 individuals from 10 families reported, some sharing the same homozygous variants (at least 4 different LoF variants reported). Sources: Expert list |
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| Mendeliome v0.1923 | IL6ST |
Zornitza Stark gene: IL6ST was added gene: IL6ST was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL6ST were set to 28747427; 30309848; 12370259; 16041381; 31914175 Phenotypes for gene: IL6ST were set to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response. Review for gene: IL6ST was set to GREEN Added comment: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association. Sources: Expert list |
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| Mendeliome v0.1917 | LIG1 |
Zornitza Stark gene: LIG1 was added gene: LIG1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIG1 were set to 30395541 Phenotypes for gene: LIG1 were set to Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis Review for gene: LIG1 was set to GREEN Added comment: Five individuals from three families. Sources: Expert list |
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| Mendeliome v0.1916 | POLE2 |
Zornitza Stark gene: POLE2 was added gene: POLE2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: POLE2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLE2 were set to 26365386 Phenotypes for gene: POLE2 were set to Combined immunodeficiency; Lymphopaenia; Lack of TRECS, absent proliferation in response to antigens; Hypoglobulinaemia; Recurrent infections, disseminated BCG infections; Autoimmunity; Facial dysmorphism Review for gene: POLE2 was set to RED Added comment: Single family reported with homozygous splice site variant. Sources: Expert list |
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| Mendeliome v0.1914 | FCHO1 |
Zornitza Stark gene: FCHO1 was added gene: FCHO1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FCHO1 were set to 32098969; 30822429 Phenotypes for gene: FCHO1 were set to Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis Review for gene: FCHO1 was set to GREEN Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data. Sources: Expert list |
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| Mendeliome v0.1913 | REL |
Zornitza Stark gene: REL was added gene: REL was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: REL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: REL were set to 31103457 Phenotypes for gene: REL were set to Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity Review for gene: REL was set to RED Added comment: Single individual from consanguineous family reported with homozygous canonical splice site variant, no functional data. Sources: Expert list |
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| Mendeliome v0.1908 | TET2 | Zornitza Stark changed review comment from: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma.; to: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1908 | TET2 | Zornitza Stark changed review comment from: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers.; to: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1908 | TET2 | Zornitza Stark changed review comment from: No evidence for Mendelian gene-disease association.; to: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1907 | RELA |
Zornitza Stark gene: RELA was added gene: RELA was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RELA were set to 28600438; 29305315 Phenotypes for gene: RELA were set to Mucocutaneous ulceration, chronic, MIM# 618287; Impaired NFkB activation; reduced production of inflammatory cytokines; autoimmune cytopaenias Review for gene: RELA was set to AMBER Added comment: Two families reported, somewhat different phenotypes. Sources: Expert list |
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| Mendeliome v0.1905 | RELB |
Zornitza Stark gene: RELB was added gene: RELB was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: RELB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RELB were set to 7834753; 26385063 Phenotypes for gene: RELB were set to Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections Review for gene: RELB was set to AMBER Added comment: Single family reported, functional data. Sources: Expert list |
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| Mendeliome v0.1901 | 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 v0.1897 | TRPA1 |
Zornitza Stark gene: TRPA1 was added gene: TRPA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TRPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPA1 were set to 20547126; 16564016; 21468319; 28314413; 24778270; 24564660; 20718100 Phenotypes for gene: TRPA1 were set to Episodic pain syndrome, familial, 1, MIM# 615040 Review for gene: TRPA1 was set to AMBER Added comment: Single family and a lot of functional data. Sources: Expert list |
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| Mendeliome v0.1896 | PLEKHA5 |
Tiong Tan gene: PLEKHA5 was added gene: PLEKHA5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PLEKHA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLEKHA5 were set to 29805042 Phenotypes for gene: PLEKHA5 were set to cleft lip; cleft palate Penetrance for gene: PLEKHA5 were set to Complete Review for gene: PLEKHA5 was set to GREEN Added comment: Sources: Literature |
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| Mendeliome v0.1894 | CNKSR1 |
Zornitza Stark gene: CNKSR1 was added gene: CNKSR1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CNKSR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CNKSR1 were set to 30450701; 30237576; 21937992 Phenotypes for gene: CNKSR1 were set to Intellectual disability Review for gene: CNKSR1 was set to AMBER Added comment: Three families reported, two as part of large cohorts reporting multiple novel genes. Note the family reported in PMID 30450701 appears to be the same family as reported in PMID 21937992. Some functional data in PMID 30450701, including Drosophila model. Sources: Expert Review |
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| Mendeliome v0.1892 | FRMD4A |
Zornitza Stark gene: FRMD4A was added gene: FRMD4A was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FRMD4A were set to 25388005; 30214071 Phenotypes for gene: FRMD4A were set to Intellectual disability; microcephaly; Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819 Review for gene: FRMD4A was set to AMBER Added comment: Single Bedouin Israeli family reported with homozygous variant initially. Good segregation data. No functional data. Another family reported as part of a large consanguineous microcephaly cohort, different variant. Sources: Expert Review |
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| Mendeliome v0.1890 | NEK10 |
Zornitza Stark gene: NEK10 was added gene: NEK10 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: NEK10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEK10 were set to 31959991 Phenotypes for gene: NEK10 were set to Primary ciliary dyskinesia; bronchiectasis Review for gene: NEK10 was set to GREEN Added comment: Nine individuals from 5 unrelated families, some functional data. Sources: NHS GMS |
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| Mendeliome v0.1888 | PIGK |
Zornitza Stark gene: PIGK was added gene: PIGK was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGK were set to 32220290 Phenotypes for gene: PIGK were set to Intellectual disability; seizures; cerebellar atrophy Review for gene: PIGK was set to GREEN Added comment: 12 individuals from 9 unrelated families reported. Sources: Literature |
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| Mendeliome v0.1886 | ADARB1 |
Zornitza Stark gene: ADARB1 was added gene: ADARB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADARB1 were set to 32220291 Phenotypes for gene: ADARB1 were set to Intellectual disability; microcephaly; seizures Review for gene: ADARB1 was set to GREEN Added comment: Four unrelated individuals with bi-allelic variants in this gene. Sources: Literature |
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| Mendeliome v0.1876 | DRP2 |
Zornitza Stark gene: DRP2 was added gene: DRP2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DRP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: DRP2 were set to 26227883; 11430802; 31217940; 22764250; 29473052 Phenotypes for gene: DRP2 were set to Charcot Marie Tooth, intermediate X-linked; HMSN Review for gene: DRP2 was set to GREEN Added comment: Three unrelated families, functional data. Sources: Expert list |
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| Mendeliome v0.1874 | DGAT2 |
Zornitza Stark gene: DGAT2 was added gene: DGAT2 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: DGAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DGAT2 were set to 26786738 Phenotypes for gene: DGAT2 were set to axonal Charcot-Marie-Tooth disease Review for gene: DGAT2 was set to AMBER Added comment: Single family (father and son) reported, with supporting in vitro functional assays and a zebrafish model. Sources: Expert Review |
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| Mendeliome v0.1872 | ERLIN1 |
Bryony Thompson gene: ERLIN1 was added gene: ERLIN1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ERLIN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERLIN1 were set to 24482476 Phenotypes for gene: ERLIN1 were set to Spastic paraplegia 62 MIM#615681 Review for gene: ERLIN1 was set to GREEN Added comment: Three unrelated consanguineous families with early onset pure HSP. Sources: Expert list |
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| Mendeliome v0.1871 | BTBD7 | Zornitza Stark Added comment: Comment when marking as ready: Agreed, no evidence currently for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1870 | NOS1AP | Zornitza Stark Added comment: Comment when marking as ready: Agreed, cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1857 | CHD3 | Zornitza Stark Added comment: Comment when marking as ready: Over 30 unrelated individuals reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1850 | FBN2 | Zornitza Stark Added comment: Comment when marking as ready: The gene-disease association with Contractual arachnodactyly is extremely well established. The gene-disease association with macular degeneration much less so. There are ~4 families reported in the literature, and some discussion about whether the contribution of rare FBN2 variants in this context are under a 'monogenic' or 'polygenic' model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1845 | AGTPBP1 |
Zornitza Stark gene: AGTPBP1 was added gene: AGTPBP1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGTPBP1 were set to 30420557 Phenotypes for gene: AGTPBP1 were set to Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276 Review for gene: AGTPBP1 was set to GREEN Added comment: Thirteen individuals with bi-allelic variants in this gene, complex neurological phenotype of dev delay/ID, cerebellar atrophy and neuropathy, severe progressive course in six. Sources: NHS GMS |
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| Mendeliome v0.1842 | ADGRG6 | Zornitza Stark edited their review of gene: ADGRG6: Added comment: Three families reported originally with severe prenatal-onset arthrogryposis (PMID: 26004201), one family with more complex neurological phenotype (PMID:30549416).; Changed rating: GREEN; Changed publications: 30549416, 26004201; Changed phenotypes: Lethal congenital contracture syndrome 9, OMIM #616503; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1841 | EIF2AK2 |
Zornitza Stark gene: EIF2AK2 was added gene: EIF2AK2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK2 were set to 32197074 Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness Review for gene: EIF2AK2 was set to GREEN Added comment: Eight individuals with de novo variants and complex neurodevelopmental phenotype. Sources: Literature |
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| Mendeliome v0.1840 | EIF2AK1 |
Zornitza Stark gene: EIF2AK1 was added gene: EIF2AK1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EIF2AK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK1 were set to 32197074 Phenotypes for gene: EIF2AK1 were set to Intellectual disability; white matter abnormalities Review for gene: EIF2AK1 was set to RED Added comment: Single individual reported with de novo variant in this gene. Sources: Literature |
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| Mendeliome v0.1838 | NOVA2 |
Zornitza Stark gene: NOVA2 was added gene: NOVA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NOVA2 were set to 32197073 Phenotypes for gene: NOVA2 were set to Intellectual disability; autism; hypotonia; spasticity; ataxia Mode of pathogenicity for gene: NOVA2 was set to Other Review for gene: NOVA2 was set to GREEN Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism. Sources: Literature |
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| Mendeliome v0.1836 | GNB2 |
Sue White gene: GNB2 was added gene: GNB2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GNB2 were set to 31698099 Phenotypes for gene: GNB2 were set to intellectual disability; dysmorphic features Penetrance for gene: GNB2 were set to Complete Review for gene: GNB2 was set to AMBER Added comment: single report of patient with de novo missense variant in GNB2 and intellectual disability. Emerging evidence of other de no missense variants in GNB2 and ID Sources: Literature |
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| Mendeliome v0.1834 | NRROS |
Sue White gene: NRROS was added gene: NRROS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NRROS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRROS were set to 32100099; 32197075 Phenotypes for gene: NRROS were set to neurodegeneration; intracranial calcification; epilepsy Penetrance for gene: NRROS were set to Complete Review for gene: NRROS was set to GREEN Added comment: normal development or mild developmental delay until onset of regression around age of 1 concurrent with epilepsy biallelic LOF mutations with functional evidence of pathogenicity Sources: Literature |
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| Mendeliome v0.1827 | HTR3C | Zornitza Stark Added comment: Comment when marking as ready: Agree no evidence for Mendelian gene-disease association currently. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1823 | SLC25A21 |
Zornitza Stark gene: SLC25A21 was added gene: SLC25A21 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: SLC25A21 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A21 were set to 29517768 Phenotypes for gene: SLC25A21 were set to Mitochondrial DNA depletion syndrome-18, MIM#618811 Review for gene: SLC25A21 was set to AMBER Added comment: One case with a homozygous variant and functional assays showing mitochondrial dysfunction. Sources: NHS GMS |
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| Mendeliome v0.1821 | SLC25A10 |
Zornitza Stark gene: SLC25A10 was added gene: SLC25A10 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: SLC25A10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A10 were set to 29211846 Phenotypes for gene: SLC25A10 were set to Intractable epileptic encephalopathy Review for gene: SLC25A10 was set to AMBER Added comment: One case with intractable epileptic encephalopathy with complex I deficiency, with biallelic variants. Yeast SLC25A10 ortholog lack-of-function causes impairment in mitochondrial respiration, reduced mtDNA copy number and oxidative stress vulnerability. Sources: NHS GMS |
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| Mendeliome v0.1815 | PTCD3 |
Zornitza Stark gene: PTCD3 was added gene: PTCD3 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTCD3 were set to 30607703; 19427859 Phenotypes for gene: PTCD3 were set to Intellectual disability; optic atrophy; Leigh-like syndrome Review for gene: PTCD3 was set to AMBER Added comment: One compound heterozygote case and functional assays. Essential subunit of oxidative phosphorylation (OXPHOS) complexes. Sources: NHS GMS |
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| Mendeliome v0.1814 | PTCD1 |
Zornitza Stark gene: PTCD1 was added gene: PTCD1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: PTCD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTCD1 were set to 25058219 Phenotypes for gene: PTCD1 were set to Cardiomyopathy Review for gene: PTCD1 was set to RED Added comment: Single case reported with no functional characterisation. Biochemical analyses of heart tissue identified global COX defect. No OMIM phenotype. Sources: NHS GMS |
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| Mendeliome v0.1809 | OXA1L |
Zornitza Stark gene: OXA1L was added gene: OXA1L was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: OXA1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OXA1L were set to 30201738; 16435202 Phenotypes for gene: OXA1L were set to Encephalopathy; hypotonia; developmental delay Review for gene: OXA1L was set to AMBER Added comment: Single family reported with biochemical and molecular analyses of patient skeletal muscle and fibroblasts. In vitro functional assays in human cell lines, Drosophila model, and yeast-based assays. Loss of function affects oxidative phosphorylation complexes IV and V. Sources: NHS GMS |
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| Mendeliome v0.1807 | NSUN3 |
Zornitza Stark gene: NSUN3 was added gene: NSUN3 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: NSUN3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSUN3 were set to 27356879 Phenotypes for gene: NSUN3 were set to combined mitochondrial respiratory chain complex deficiency Review for gene: NSUN3 was set to AMBER Added comment: A single compound heterozygous case. Patient-derived fibroblasts exhibited severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. In vitro functional assays also conducted. Sources: NHS GMS |
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| Mendeliome v0.1805 | NDUFB10 |
Zornitza Stark gene: NDUFB10 was added gene: NDUFB10 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: NDUFB10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFB10 were set to 28040730; 32025618 Phenotypes for gene: NDUFB10 were set to fatal infantile lactic acidosis; cardiomyopathy Review for gene: NDUFB10 was set to AMBER Added comment: Single compound heterozygote case and mitochondrial phenotype. Assays of respiratory chain enzyme activities and functions in patient tissues/fibroblasts and in vitro functional assays. Plant model system supporting mitochondrial complex I dysfunction. Sources: NHS GMS |
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| Mendeliome v0.1803 | NDUFA4 | Zornitza Stark changed review comment from: Single family and a lot of functional data. Encodes a complex IV subunit.; to: Single family and a lot of functional data. Unpublished data on another family. Encodes a complex IV subunit. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1801 | MRM2 |
Zornitza Stark gene: MRM2 was added gene: MRM2 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRM2 were set to 28973171 Phenotypes for gene: MRM2 were set to MELAS-like Review for gene: MRM2 was set to AMBER Added comment: Single individual reported plus functional data. MRM2 encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA. Sources: NHS GMS |
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| Mendeliome v0.1799 | MRPL3 | Zornitza Stark changed review comment from: 1 French family with 4 sibs with severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies. 1 male infant with a severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies.; to: 1 French family with 4 sibs with severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, some functional studies. 1 male infant with a severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1798 | IDH3A |
Zornitza Stark gene: IDH3A was added gene: IDH3A was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: IDH3A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IDH3A were set to 31012789; 30478029; 30058936; 28412069 Phenotypes for gene: IDH3A were set to Retinitis pigmentosa Review for gene: IDH3A was set to GREEN Added comment: Six unrelated families reported with retinitis pigmentosa. Mouse model. Sources: NHS GMS |
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| Mendeliome v0.1797 | GATC |
Zornitza Stark gene: GATC was added gene: GATC was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: GATC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GATC were set to 30283131 Phenotypes for gene: GATC were set to Mitochondrial cardiomyopathy Review for gene: GATC was set to RED Added comment: Two families with 6 affected individuals reported; same homozygous variant. Sources: NHS GMS |
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| Mendeliome v0.1796 | GATB |
Zornitza Stark gene: GATB was added gene: GATB was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: GATB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GATB were set to 30283131 Phenotypes for gene: GATB were set to Mitochondrial cardiomyopathy Review for gene: GATB was set to RED Added comment: Single family reported with two affected siblings Sources: NHS GMS |
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| Mendeliome v0.1795 | FECH | Zornitza Stark Added comment: Comment when marking as ready: Evidence for dominant disease is limited. Please note there is a common, hypomorphic deep intronic variant, IVS3-48T-C, as well as an exon 10 deletion reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1792 | ADAM17 | Zornitza Stark Added comment: Comment when marking as ready: Two families and a mouse model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1788 | ZNF462 | Zornitza Stark Added comment: Comment when marking as ready: Multiple congenital anomaly syndrome characterised by variable but usually mild global developmental delay and common craniofacial abnormalities, including ptosis, abnormal head shape, downslanting palpebral fissures, epicanthal folds, arched eyebrows, and short upturned nose. Many patients have hypotonia and feeding difficulties. A few patients show agenesis of the corpus callosum on brain imaging. Most cases occur sporadically, but there are rare familial cases that show highly variable expressivity in the phenotypic manifestations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1781 | TFAM |
Zornitza Stark gene: TFAM was added gene: TFAM was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TFAM were set to 27448789; 29021295; 9500544 Phenotypes for gene: TFAM were set to Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156 Review for gene: TFAM was set to AMBER Added comment: One consanguineous family segregates a homozygous variant. Tfam knockout mouse has a mitochondrial cardiomyopathy phenotype and severe mtDNA depletion with abolished oxidative phosphorylation. Sources: NHS GMS |
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| Mendeliome v0.1779 | TIMM22 |
Zornitza Stark gene: TIMM22 was added gene: TIMM22 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TIMM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMM22 were set to 30452684 Phenotypes for gene: TIMM22 were set to mitochondrial myopathy; hypotonia; gastroesophageal reflux disease Review for gene: TIMM22 was set to AMBER Added comment: One compound heterozygote case identified with supporting in vitro and patient cell functional assays. Sources: NHS GMS |
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| Mendeliome v0.1777 | TIMMDC1 |
Zornitza Stark gene: TIMMDC1 was added gene: TIMMDC1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMMDC1 were set to 28604674; 30981218 Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31 MIM#618251 Review for gene: TIMMDC1 was set to AMBER Added comment: A deep intronic variant (c.597-1340A>G, only detectable by WGS) that causes a splicing aberration was identified in a homozygous state in 3 unrelated cases from different ethnic backgrounds. A patient with Leigh-like syndrome had a homozygous stopgain variant in PDHX and a homozygous stopgain variant in TIMMDC1 (p.Arg225*). The TIMMDC1 mutant protein could still rescue complex I assembly in TIMMDC1 knockout cells and the patient’s clinical phenotype was not clearly distinct from that of other patients with the same PDHX defect. Sources: NHS GMS |
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| Mendeliome v0.1775 | TMEM65 |
Zornitza Stark gene: TMEM65 was added gene: TMEM65 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TMEM65 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM65 were set to 28295037 Phenotypes for gene: TMEM65 were set to Mitochondrial encephalomyopathy Review for gene: TMEM65 was set to AMBER Added comment: One homozygous case with a mitochondrial encephalomyopathy and functional assays showing the protein is important for mitochondrial respiration and mtDNA copy number maintenance. Sources: NHS GMS |
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| Mendeliome v0.1773 | SSBP1 |
Bryony Thompson gene: SSBP1 was added gene: SSBP1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: SSBP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SSBP1 were set to 31298765; 31479473; 31550237; 31550240 Phenotypes for gene: SSBP1 were set to Optic atrophy with or without extraocular phenotypes Review for gene: SSBP1 was set to GREEN Added comment: At least 9 dominant families/cases and 1 recessive with optic atrophy with/without additional clinical features, including retinal macular dystrophy, sensorineural deafness, mitochondrial myopathy, and kidney failure. Supporting evidence in functional assays and zebrafish model. Sources: NHS GMS |
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| Mendeliome v0.1771 | COX6A2 |
Zornitza Stark gene: COX6A2 was added gene: COX6A2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: COX6A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX6A2 were set to 31155743; 23460811 Phenotypes for gene: COX6A2 were set to Mitochondrial complex IV deficiency, MIM# 220110 Review for gene: COX6A2 was set to GREEN Added comment: Two unrelated families and two mouse models. Sources: Expert list |
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| Mendeliome v0.1769 | YME1L1 |
Zornitza Stark gene: YME1L1 was added gene: YME1L1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: YME1L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YME1L1 were set to 30544562; 27495975 Phenotypes for gene: YME1L1 were set to Optic atrophy 11, MIM#617302 Review for gene: YME1L1 was set to AMBER Added comment: One consanguineous family with a homozygous variant and functional assays. YME1L leads to mitochondrial fragmentation and severely disorganized and attenuated cristae architecture in in vitro functional assays. Sources: NHS GMS |
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| Mendeliome v0.1766 | ANXA11 |
Bryony Thompson gene: ANXA11 was added gene: ANXA11 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ANXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ANXA11 were set to 28469040; 29845112; 30109997 Phenotypes for gene: ANXA11 were set to Amytrophic lateral sclerosis 23 MIM#617839 Review for gene: ANXA11 was set to GREEN Added comment: 4 different missense variants in 10 patients from 7 unrelated families with amyotrophic lateral sclerosis and functional assays supporting association. Sources: Expert list |
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| Mendeliome v0.1744 | 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 v0.1727 | NADK2 |
Zornitza Stark gene: NADK2 was added gene: NADK2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NADK2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NADK2 were set to 24847004; 29388319; 27940755 Phenotypes for gene: NADK2 were set to 2,4-dienoyl-CoA reductase deficiency, MIM# 616034 Review for gene: NADK2 was set to GREEN gene: NADK2 was marked as current diagnostic Added comment: Mitochondrial dysfunction resulting in severe neurologic and metabolic dysfunction beginning in early infancy reported in two individuals with confirmed variants in this gene. Another individual with homozygous hypomorphic start loss variant g.36241900 A>G p. Met1Val and milder phenotype reported (PMID:29388319). Sources: Expert list |
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| Mendeliome v0.1725 | ISCA1 |
Zornitza Stark gene: ISCA1 was added gene: ISCA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISCA1 were set to 28356563; 32092383; 31016283; 30113620; 30105122 Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613 Review for gene: ISCA1 was set to GREEN gene: ISCA1 was marked as current diagnostic Added comment: Multiple unrelated families reported. Severe disorder characterised by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Rat model results in early lethality. Founder variant c.259G > A, p.(Glu87Lys) reported in Indian families. Sources: Expert list |
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| Mendeliome v0.1714 | CTNNB1 |
Teresa Zhao changed review comment from: OMIM: LoF - mainly non cancerous phenotypes, and GoF - mainly cancer phenotypes. Cancer hot spot in exon 3, mainly missenses affecting S33, S37, S45, T41, D32 and G34 (Gao. C. et al. 2017); to: OMIM: LoF - mainly non cancerous phenotypes, and GoF - mainly cancer phenotypes. Cancer hot spot in exon 3, mainly missenses affecting S33, S37, S45, T41, D32 and G34 (Gao. C. et al. 2017) |
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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 v0.1703 | IFT74 | Zornitza Stark edited their review of gene: IFT74: Added comment: Second individual with bi-allelic variants and BBS phenotype reported.; Changed rating: GREEN; Changed publications: 27486776, 32144365 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1699 | TNNI3K |
Zornitza Stark gene: TNNI3K was added gene: TNNI3K was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TNNI3K was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TNNI3K were set to 30010057; 29355681 Phenotypes for gene: TNNI3K were set to Cardiac conduction disease with or without dilated cardiomyopathy, MIM# 616117 Review for gene: TNNI3K was set to GREEN gene: TNNI3K was marked as current diagnostic Added comment: At least 6 multigenerational families reported where variants segregated with disease. Sources: Expert list |
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| Mendeliome v0.1692 | PPM1E | Zornitza Stark Added comment: Comment when marking as ready: Agreed, cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1685 | CXorf56 | Zornitza Stark edited their review of gene: CXorf56: Added comment: Additional 3 families reported, upgrade to Green.; Changed rating: GREEN; Changed publications: 29374277, 31822863; Changed phenotypes: Mental retardation, X-linked 107, MIM# 301013 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1673 | KANK1 | Zornitza Stark changed review comment from: Comment on list classification: Amber for nephrotic after discussion with Chirag Patel.; to: Comment on list classification: Red for nephrotic after discussion with Chirag Patel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1659 | MED12L |
Zornitza Stark gene: MED12L was added gene: MED12L was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MED12L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MED12L were set to 31155615 Phenotypes for gene: MED12L were set to Intellectual disability; Seizures; Autism Review for gene: MED12L was set to GREEN Added comment: 7 individuals reported, 3 with CNVs (encompassing other genes) and 4 with SNVs (frameshift, nonsense and splice site). Sources: Expert list |
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| Mendeliome v0.1657 | MCM3AP |
Zornitza Stark gene: MCM3AP was added gene: MCM3AP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295 Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, MIM#618124 Review for gene: MCM3AP was set to GREEN gene: MCM3AP was marked as current diagnostic Added comment: At least 10 families reported. Sources: Expert list |
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| Mendeliome v0.1656 | MAPRE2 | Zornitza Stark Phenotypes for gene: MAPRE2 were changed from to Symmetric circumferential skin creases, congenital, 2, MIM# 616734 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1653 | MAPRE2 | Zornitza Stark reviewed gene: MAPRE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26637975; Phenotypes: Symmetric circumferential skin creases, congenital, 2, MIM# 616734; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1636 | NUDT2 |
Zornitza Stark gene: NUDT2 was added gene: NUDT2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUDT2 were set to 27431290; 30059600 Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability Review for gene: NUDT2 was set to AMBER Added comment: 7 affected individuals from 4 Saudi families, with same homozygous truncating variant. Sources: Expert list |
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| Mendeliome v0.1634 | NKAP |
Zornitza Stark gene: NKAP was added gene: NKAP was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NKAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NKAP were set to 26358559; 26350204; 31587868 Phenotypes for gene: NKAP were set to Intellectual disability Review for gene: NKAP was set to GREEN gene: NKAP was marked as current diagnostic Added comment: 10 males from 8 unrelated families with missense mutations in NKAP (on Xq24) Hypotonia and tall stature with Marfanoid habitus was predominant phenotype. One variant (NM_024528:c.988G>A / p.Arg333Gln) Sources: Expert list |
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| Mendeliome v0.1562 | SPOP |
Zornitza Stark gene: SPOP was added gene: SPOP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPOP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPOP were set to 32109420 Phenotypes for gene: SPOP were set to Intellectual disability; dysmorphism; microcephaly; macrocephaly Mode of pathogenicity for gene: SPOP was set to Other Review for gene: SPOP was set to GREEN Added comment: Seven individuals reported with de novo missense variants in this gene. Gain-of-function variants associated with microcephaly whereas dominant-negative variants associated with macrocephaly. Sources: Literature |
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| Mendeliome v0.1553 | 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 v0.1505 | SLC52A1 | Zornitza Stark Added comment: Comment when marking as ready: Essentially only one family. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1496 | ZNF592 |
Chern Lim changed review comment from: No patients reported with ZNF592 variant that is clearly disease causing. A 2010 paper published a biallelic missense variant segregating in one family with non-progressive, autosomal recessive, congenital cerebellar ataxia; however functional data not strongly supportive of pathogenicity (PMID: 20531441). Same authors later identified a homozygous WDR73 variant in that family which explains the phenotype (PMID: 26123727).; to: No patients reported with ZNF592 variant that is clearly disease causing. A 2010 paper published a biallelic missense variant segregating in one family with non-progressive, autosomal recessive, congenital cerebellar ataxia; however functional data not strongly conclusive for pathogenicity (PMID: 20531441). Same authors later identified a homozygous WDR73 variant in that family which explains the phenotype (PMID: 26123727). |
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| Mendeliome v0.1487 | CYP21A2 | Zornitza Stark Added comment: Comment when marking as ready: Beware pseudogene and structural variants make NGS data difficult to interpret. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1479 | FMO3 | Zornitza Stark changed review comment from: Comment when marking as ready: Inborn error of metabolism accompanied by fish-like body odor resulting from deficiency of dimethylglycine dehydrogenase; to: Comment when marking as ready: Inborn error of metabolism accompanied by fish-like body odour resulting from deficiency of dimethylglycine dehydrogenase | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1479 | FMO3 | Zornitza Stark Added comment: Comment when marking as ready: Inborn error of metabolism accompanied by fish-like body odor resulting from deficiency of dimethylglycine dehydrogenase | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1473 | CEP135 | Elena Savva Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1473 | CEP135 |
Elena Savva changed review comment from: Microcephalic primordial dwarfism - single case Incomplete NMD shown, LOF mechanism; to: Microcephalic primordial dwarfism - single case Incomplete NMD shown, LOF mechanism |
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| Mendeliome v0.1473 | CEP85L |
Zornitza Stark gene: CEP85L was added gene: CEP85L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CEP85L were set to 32097630 Phenotypes for gene: CEP85L were set to Lissencephaly, posterior predominant Review for gene: CEP85L was set to GREEN Added comment: Thirteen individuals reported with mono allelic variants in this gene, inherited in two of the families. Mouse model had neuronal migration defects. Sources: Literature |
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| Mendeliome v0.1471 | COX4I2 | Zornitza Stark edited their review of gene: COX4I2: Added comment: Glu138Lys present in 3 homozygotes in gnomad, wich is out of keeping for this rare metabolic disorder. Note no other variants reported in this gene since original report in 2009. All variants submitted to ClinVar are VOUS/LB/B.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1443 | ARSG |
Zornitza Stark gene: ARSG was added gene: ARSG was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ARSG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARSG were set to 29300381; 20679209; 25452429; 26975023 Phenotypes for gene: ARSG were set to Usher syndrome, type IV, MIM# 618144 Review for gene: ARSG was set to RED Added comment: Atypical late-onset RP/HL phenotype described in 5 individuals from three Yemenite Jewish families. Same homozygous missense variant identified in all, founder effect. Animal models associated with neuronal ceroid lipofuscinosis. Sources: Expert list |
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| Mendeliome v0.1438 | MYL1 |
Bryony Thompson gene: MYL1 was added gene: MYL1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYL1 were set to 30215711 Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy MIM#618414 Review for gene: MYL1 was set to AMBER Added comment: Two probands with congenital myopathy and a zebrafish model. Probably need one more family to push it over the line. Sources: NHS GMS |
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| Mendeliome v0.1437 | FXR1 | Bryony Thompson Added comment: Comment on list classification: Only two families, but a lot of functional supporting evidence including a mouse model. Pathogenic variants likely to be found in exon 15 of the skeletal muscle isoform, specifically. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1435 | WDR81 | Kristin Rigbye changed review comment from: A homozygous and compound heterozygous nonsense and missense variants reported. Variants shown to result in a loss of function (PMID: 28969387).; to: Homozygous and compound heterozygous nonsense and missense variants reported. Variants shown to result in a loss of function (PMID: 28969387). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1435 | WDR81 | Kristin Rigbye changed review comment from: A few homozygous families reported to date. Variants are expected to results in a loss of function, although functional studies have not been performed.; to: A homozygous and compound heterozygous nonsense and missense variants reported. Variants shown to result in a loss of function (PMID: 28969387). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1418 | PNPT1 | Zornitza Stark Added comment: Comment when marking as ready: Those initially presenting with deafness may be at risk of progressive complex neurological course. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1374 | UGT1A4 | Zornitza Stark Added comment: Comment when marking as ready: Agree, no evidence currently for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1365 | AKT1 | Zornitza Stark Mode of pathogenicity for gene: AKT1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1357 | AKT1 | Elena Savva reviewed gene: AKT1: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 23246288; Phenotypes: Cowden syndrome 6, Proteus syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1347 | PLEKHG2 | Zornitza Stark edited their review of gene: PLEKHG2: Added comment: Further family identified, promote to Amber.; Changed rating: AMBER; Changed publications: 26539891, 24001768, 26573021; Changed phenotypes: Leukodystrophy and acquired microcephaly with or without dystonia, MIM# 616763 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1339 | TOR1AIP1 | Bryony Thompson Added comment: Comment on list classification: Phenotype appears to be variable depending on which isoform is affected by the variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1338 | TOR1AIP1 |
Bryony Thompson gene: TOR1AIP1 was added gene: TOR1AIP1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937 Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072 Review for gene: TOR1AIP1 was set to GREEN Added comment: At least 5 families/cases reported with muscular dystrophy and sometimes cardiomyopathy. Sources: Expert list |
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| Mendeliome v0.1333 | 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 v0.1289 | AHI1 | Elena Savva commented on gene: AHI1: Functional assays using zebrafish model support that the C-terminal SH3 domain is not required (PMID: 25616960) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1273 | GRIA1 |
Zornitza Stark gene: GRIA1 was added gene: GRIA1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GRIA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178 Phenotypes for gene: GRIA1 were set to Intellectual disability; autism Review for gene: GRIA1 was set to GREEN Added comment: Multiple affected individuals reported but in large ID cohorts reporting multiple candidate genes. Recurrent (p.A636T) variant. Sources: Expert list |
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| Mendeliome v0.1271 | HDAC4 | Zornitza Stark changed review comment from: Comment when marking as ready: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only reports of intragenic variants (still structural rather than SNVs).; to: Comment when marking as ready: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only two reports of intragenic variants (still structural rather than SNVs). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1271 | HDAC4 | Zornitza Stark Added comment: Comment when marking as ready: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only reports of intragenic variants (still structural rather than SNVs). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1258 | TRAPPC4 |
Zornitza Stark gene: TRAPPC4 was added gene: TRAPPC4 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: TRAPPC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC4 were set to 31794024 Phenotypes for gene: TRAPPC4 were set to intellectual disability; epilepsy; spasticity; microcephaly Review for gene: TRAPPC4 was set to GREEN Added comment: Seven individuals from three unrelated families reported; recurrent splice site variant (hg19:chr11:g.118890966A>G; TRAPPC4: NM_016146.5; c.454+3A>G), not a founder variant. Sources: Expert Review |
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| Mendeliome v0.1256 | SNX27 |
Zornitza Stark gene: SNX27 was added gene: SNX27 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: SNX27 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNX27 were set to 25894286; 31721175; 21300787; 23524343 Phenotypes for gene: SNX27 were set to intellectual disability; seizures Review for gene: SNX27 was set to GREEN Added comment: Three unrelated families and animal model. Sources: Expert Review |
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| Mendeliome v0.1254 | NSF |
Zornitza Stark gene: NSF was added gene: NSF was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NSF were set to 31675180 Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability Review for gene: NSF was set to AMBER Added comment: Two individuals reported with de novo missense variants in this gene. Sources: Literature |
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| Mendeliome v0.1252 | KAT8 |
Zornitza Stark gene: KAT8 was added gene: KAT8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KAT8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KAT8 were set to 31794431 Phenotypes for gene: KAT8 were set to Intellectual disability; seizures; autism; dysmorphic features Review for gene: KAT8 was set to GREEN Added comment: Eight unrelated individuals reported with de novo variants in this gene and a mouse model. All variants missense, in the chromobarrel domain or the acetyltransferase domain; three individuals had the same variant p.Tyr90Cys . One more individual reported with bi-allelic variants: one missense and one frameshift; carrier parents were normal suggesting that may be haploinsuffiency is not the mechanism. Sources: Literature |
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| Mendeliome v0.1231 | ACTB | Sebastian Lunke Added comment: Comment on mode of pathogenicity: Both GoF and LoF described | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1226 | GCKR | Sebastian Lunke Added comment: Comment on mode of inheritance: Risk factor only | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.1150 | 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 v0.1148 | DIP2B | Zornitza Stark Mode of pathogenicity for gene: DIP2B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1145 | DIP2B | Zornitza Stark reviewed gene: DIP2B: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 17236128; Phenotypes: Mental retardation, FRA12A type, MIM# 136630; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1144 | DCPS |
Zornitza Stark gene: DCPS was added gene: DCPS was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DCPS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DCPS were set to 25701870; 30289615; 25712129 Phenotypes for gene: DCPS were set to Al-Raqad syndrome, MIM#616459 Review for gene: DCPS was set to GREEN gene: DCPS was marked as current diagnostic Added comment: 7 individuals from 3 families reported. Sources: Expert list |
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| Mendeliome v0.1142 | CUX1 |
Zornitza Stark gene: CUX1 was added gene: CUX1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CUX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CUX1 were set to 25059644; 20510857; 30014507 Phenotypes for gene: CUX1 were set to Global developmental delay with or without impaired intellectual development, 618330 Review for gene: CUX1 was set to GREEN gene: CUX1 was marked as current diagnostic Added comment: Nine individuals from 7 families reported. Three individuals had normal intelligence at school age despite significant early developmental delay. Sources: Expert list |
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| Mendeliome v0.1124 | SDR9C7 |
Zornitza Stark gene: SDR9C7 was added gene: SDR9C7 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SDR9C7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SDR9C7 were set to 28173123; 28369735 Phenotypes for gene: SDR9C7 were set to Ichthyosis, congenital, autosomal recessive 13 MIM#617574 Review for gene: SDR9C7 was set to GREEN Added comment: Three homozygous variants in 4 families with congenital ichthyosis. Sources: Expert list |
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| Mendeliome v0.1120 | RBBP8 | Zornitza Stark Added comment: Comment when marking as ready: Individuals from 3 families reported in the literature with bi-allelic variants in this gene: clinical diagnosis was Jawad syndrome in one, and Seckel syndrome in 2. ID is a reported feature. Additional variant in ClinVar, so overall rating Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1100 | CACNA2D3 | Zornitza Stark Added comment: Comment when marking as ready: Agree no evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1091 | CASP14 |
Zornitza Stark gene: CASP14 was added gene: CASP14 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CASP14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CASP14 were set to 27494380; 23014340; 17515931 Phenotypes for gene: CASP14 were set to Ichthyosis, congenital, autosomal recessive 12 MIM#617320 Review for gene: CASP14 was set to AMBER Added comment: The same 2bp deletion was identified in 3 patients with a mild form of generalised ichthyosis from 2 Algerian families. Casp14-/- mouse models had prominent dermatological features. Sources: Expert Review |
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| Mendeliome v0.1069 | 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 v0.1054 | SLC52A1 | Kristin Rigbye Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1054 | PTCH2 | Kristin Rigbye Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1030 | SLC52A1 | Kristin Rigbye commented on gene: SLC52A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1030 | PTCH2 | Kristin Rigbye commented on gene: PTCH2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1025 | MYRF |
Zornitza Stark gene: MYRF was added gene: MYRF was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MYRF were set to 31048900; 31172260; 31266062; 31700225 Phenotypes for gene: MYRF were set to Nanophthalmos; High hyperopia Review for gene: MYRF was set to GREEN gene: MYRF was marked as current diagnostic Added comment: Multiple affected individuals reported. 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 v0.1016 | MAB21L1 |
Sue White gene: MAB21L1 was added gene: MAB21L1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAB21L1 were set to 30487245 Phenotypes for gene: MAB21L1 were set to Cerebellar, ocular, craniofacial, and genital syndrome #MIM 618479 Penetrance for gene: MAB21L1 were set to Complete Review for gene: MAB21L1 was set to GREEN Added comment: Sources: Literature |
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| Mendeliome v0.1001 | ATP6V1C2 |
Zornitza Stark gene: ATP6V1C2 was added gene: ATP6V1C2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATP6V1C2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP6V1C2 were set to 31959358 Phenotypes for gene: ATP6V1C2 were set to Distal renal tubular acidosis Review for gene: ATP6V1C2 was set to RED Added comment: Single family reported, limited functional data. Sources: Literature |
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| Mendeliome v0.992 | HCN2 | Zornitza Stark edited their review of gene: HCN2: Added comment: Further cases identified. Evidence for both mono-allelic and bi-allelic variants causing disease; also evidence for both GoF and LoF as mechanism.; Changed rating: GREEN; Changed publications: 22131395, 30986657, 29064616, 20437590, 12514127, 17931874; Changed phenotypes: Genetic epilepsy with febrile seizures plus, Other seizure disorders; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.989 | AGO1 |
Zornitza Stark gene: AGO1 was added gene: AGO1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AGO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AGO1 were set to 30213762; 22495306; 23020937; 25363768; 25356899; 27620904; 29346770; 28135719 Phenotypes for gene: AGO1 were set to Intellectual disability; autism Review for gene: AGO1 was set to GREEN Added comment: Multiple individuals reported with de novo variants in this gene, most as part of large ID cohorts so phenotypic information is scarce; however, given large number I have rated as Green. Sources: Expert list |
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| Mendeliome v0.987 | CNOT2 |
Sebastian Lunke gene: CNOT2 was added gene: CNOT2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719 Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies 618608 Review for gene: CNOT2 was set to GREEN gene: CNOT2 was marked as current diagnostic Added comment: From GEL: Three independent patients with non-sense or intra-genic deletions 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 v0.951 | NBEA |
Zornitza Stark gene: NBEA was added gene: NBEA was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NBEA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NBEA were set to 30269351; 28554332; 12746398; 12826745; 11450821; 3377648; 23277425; 22109531; 23153818 Phenotypes for gene: NBEA were set to Intellectual disability; Seizures Review for gene: NBEA was set to GREEN gene: NBEA was marked as current diagnostic Added comment: 24 de novo variants reported in individuals with a neurodevelopmental disorder Sources: Expert list |
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| Mendeliome v0.949 | MACF1 |
Zornitza Stark gene: MACF1 was added gene: MACF1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MACF1 were set to 30471716 Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation, MIM# 618325 Mode of pathogenicity for gene: MACF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: MACF1 was set to GREEN Added comment: Nine individuals (including a pair of twins) reported with de novo variants in this gene. 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 v0.914 | RAB11A |
Zornitza Stark gene: RAB11A was added gene: RAB11A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RAB11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB11A were set to 29100083 Phenotypes for gene: RAB11A were set to Intellectual disability; seizures Review for gene: RAB11A was set to AMBER Added comment: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated. Sources: Literature |
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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 v0.899 | FGF16 |
Zornitza Stark gene: FGF16 was added gene: FGF16 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FGF16 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FGF16 were set to Metacarpal 4-5 fusion, MIM# 309630 Review for gene: FGF16 was set to GREEN gene: FGF16 was marked as current diagnostic Added comment: 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 v0.869 | FOXJ1 | Zornitza Stark Phenotypes for gene: FOXJ1 were changed from to hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.866 | FOXJ1 | Zornitza Stark reviewed gene: FOXJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31630787; Phenotypes: hydrocephalus, chronic destructive airway disease, randomization of left/right body asymmetry; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.839 | ADCY8 | Zornitza Stark Added comment: Comment when marking as ready: Cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.833 | ACAN |
Zornitza Stark gene: ACAN was added gene: ACAN was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ACAN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: ACAN were set to Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800; Spondyloepimetaphyseal dysplasia, aggrecan type 612813 Review for gene: ACAN was set to GREEN Added comment: Sources: Expert list |
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| Mendeliome v0.831 | NKX2-2 |
Zornitza Stark gene: NKX2-2 was added gene: NKX2-2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: NKX2-2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NKX2-2 were set to 24411943; 9584121 Phenotypes for gene: NKX2-2 were set to Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment Review for gene: NKX2-2 was set to GREEN Added comment: Sources: Expert list |
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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 v0.818 | MAPK8IP3 |
Zornitza Stark gene: MAPK8IP3 was added gene: MAPK8IP3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAPK8IP3 were set to 30612693 Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities OMIM# 605431 Review for gene: MAPK8IP3 was set to GREEN Added comment: >3 reported individuals and functional evidence in Caenorhabditis elegans Sources: Literature |
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| Mendeliome v0.816 | NCAPG2 |
Zornitza Stark gene: NCAPG2 was added gene: NCAPG2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NCAPG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NCAPG2 were set to 30609410 Phenotypes for gene: NCAPG2 were set to Khan-Khan-Katsanis syndrome, MIM# 618460 Review for gene: NCAPG2 was set to GREEN Added comment: Two families and functional evidence (zebrafish model). 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 v0.812 | RIC1 |
Zornitza Stark gene: RIC1 was added gene: RIC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RIC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RIC1 were set to 31932796 Phenotypes for gene: RIC1 were set to Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD Review for gene: RIC1 was set to AMBER Added comment: Zebrafish model and consanguineous families but homozygous-by-descent. 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 v0.806 | SIX2 | Zornitza Stark Added comment: Comment when marking as ready: Single family reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.802 | SRGAP1 | Zornitza Stark Added comment: Comment when marking as ready: Two families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.797 | TET3 |
Zornitza Stark gene: TET3 was added gene: TET3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TET3 were set to 31928709 Phenotypes for gene: TET3 were set to Intellectual disability; dysmorphic features; abnormal growth; movement disorders Review for gene: TET3 was set to GREEN Added comment: Eleven individuals from 8 families described. Mono-allelic frameshift and nonsense variants occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues; all but one such variant occur within the catalytic domain, and most display hypomorphic function in an assay of catalytic activity. Sources: Literature |
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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 v0.785 | SLC35A3 |
Zornitza Stark Added comment: Comment when marking as ready: 1 family with 2 sibs, with segregation but no functional studies. 1 family with 8 affected people. The mutations segregated with the disorder in the family. Patient cells showed no normal transcript, indicating that they had no functional SLC35A3 protein. Golgi vesicles derived from patient fibroblasts showed significantly reduced transport of UDP-GlCNAc compared to controls. |
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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 v0.777 | ZC3H14 | Zornitza Stark Added comment: Comment when marking as ready: Two families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.774 | ZFHX3 | Zornitza Stark Added comment: Comment when marking as ready: Emerging evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.773 | ZFHX3 | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.773 | KLLN | Zornitza Stark Added comment: Comment when marking as ready: Epigenetic modification of the promoter linked to Cowden syndrome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.769 | MDH1 |
Zornitza Stark gene: MDH1 was added gene: MDH1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: MDH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MDH1 were set to 31538237 Phenotypes for gene: MDH1 were set to epilepsy; microcephaly; intellectual disability Review for gene: MDH1 was set to AMBER Added comment: single consanguinous family with biallelic missense variant in this gene and epilepsy, microcephaly, ID; some functional data. Sources: Literature |
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| Mendeliome v0.767 | ISLR2 |
Zornitza Stark gene: ISLR2 was added gene: ISLR2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ISLR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISLR2 were set to 30483960 Phenotypes for gene: ISLR2 were set to hydrocephalus; arthrogryposis; abdominal distension Review for gene: ISLR2 was set to AMBER Added comment: single consanguineous family with hydrocephalus and arthrogryposis and homozygous truncating variant, mouse model has hydrocephalus Sources: Literature |
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| Mendeliome v0.765 | AGMO |
Sue White gene: AGMO was added gene: AGMO was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGMO were set to 31555905 Phenotypes for gene: AGMO were set to microcephaly; intellectual disability; epilepsy Penetrance for gene: AGMO were set to Complete Review for gene: AGMO was set to GREEN Added comment: biallelic LOF and missense reported Sources: Literature |
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| Mendeliome v0.763 | NOTCH2NL |
Sue White gene: NOTCH2NL was added gene: NOTCH2NL was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NOTCH2NL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NOTCH2NL were set to 31332381 Phenotypes for gene: NOTCH2NL were set to OMIM 603472 NEURONAL INTRANUCLEAR INCLUSION DISEASE; NIID Penetrance for gene: NOTCH2NL were set to unknown Mode of pathogenicity for gene: NOTCH2NL was set to Other Review for gene: NOTCH2NL was set to GREEN gene: NOTCH2NL was marked as current diagnostic Added comment: adult onset neurodegenerative condition caused by STR expansion 5' of NOTCH2NL Sources: Literature |
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| Mendeliome v0.761 | RFC1 |
Sue White gene: RFC1 was added gene: RFC1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: RFC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RFC1 were set to 30926972 Phenotypes for gene: RFC1 were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575 Penetrance for gene: RFC1 were set to unknown Mode of pathogenicity for gene: RFC1 was set to Other Review for gene: RFC1 was set to GREEN Added comment: adult onset ataxia due to biallelic intronic STR expansion Sources: Literature |
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| Mendeliome v0.756 | TRAC |
Zornitza Stark gene: TRAC was added gene: TRAC was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: TRAC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAC were set to 21206088 Phenotypes for gene: TRAC were set to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387 Review for gene: TRAC was set to GREEN Added comment: Sources: Expert list |
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| Mendeliome v0.750 | MYSM1 |
Zornitza Stark gene: MYSM1 was added gene: MYSM1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: MYSM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYSM1 were set to 4288411; 28115216; 26220525 Phenotypes for gene: MYSM1 were set to Bone marrow failure syndrome 4, MIM#618116 Review for gene: MYSM1 was set to GREEN Added comment: early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay Sources: Expert list |
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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 v0.742 | MESD |
Zornitza Stark gene: MESD was added gene: MESD was added to Mendeliome_VCGS. Sources: Other Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESD were set to 31564437 Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, MIM# 618644 Review for gene: MESD was set to GREEN Added comment: Five families reported. 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 v0.720 | TNS2 |
Zornitza Stark gene: TNS2 was added gene: TNS2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: TNS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNS2 were set to 29773874 Phenotypes for gene: TNS2 were set to Nephrotic syndrome Review for gene: TNS2 was set to GREEN Added comment: Five families reported in this paper reporting multiple new SRNS genes. Sources: Expert list |
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| Mendeliome v0.717 | DNASE2 |
Zornitza Stark gene: DNASE2 was added gene: DNASE2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNASE2 were set to 29259162; 31775019 Phenotypes for gene: DNASE2 were set to Auto-inflammatory disorder; splenomegaly; glomerulonephritis; liver fibrosis; arthritis; HLH Review for gene: DNASE2 was set to GREEN Added comment: Inflammatory disorder characterized by splenomegaly, glomerulonephritis, liver fibrosis, circulating anti-DNA autoantibodies, and progressive arthritis. Three families and functional data. Sources: Expert list |
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| Mendeliome v0.715 | IGHM |
Zornitza Stark gene: IGHM was added gene: IGHM was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: IGHM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IGHM were set to 12370281; 8890099 Phenotypes for gene: IGHM were set to Agammaglobulinemia 1, MIM# 601495 Review for gene: IGHM was set to GREEN Added comment: Multiple families reported; please note a 40kb deletion as well as SNVs. Sources: Expert list |
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| Mendeliome v0.709 | NUP214 |
Sue White gene: NUP214 was added gene: NUP214 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NUP214 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP214 were set to 31178128 Phenotypes for gene: NUP214 were set to epileptic encephalopathy; developmental regression; microcephaly Penetrance for gene: NUP214 were set to Complete Review for gene: NUP214 was set to GREEN gene: NUP214 was marked as current diagnostic Added comment: Sources: Literature |
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| Mendeliome v0.707 | ATP2B2 |
Sue White gene: ATP2B2 was added gene: ATP2B2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ATP2B2 were set to progressive sensorineural deafness Penetrance for gene: ATP2B2 were set to unknown Review for gene: ATP2B2 was set to GREEN gene: ATP2B2 was marked as current diagnostic Added comment: Sources: Literature |
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| Mendeliome v0.705 | NPM1 |
Sue White gene: NPM1 was added gene: NPM1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NPM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NPM1 were set to 31570891 Phenotypes for gene: NPM1 were set to radial ray defects; short stature; nail dsytrophy; bone marrow failure Penetrance for gene: NPM1 were set to unknown Review for gene: NPM1 was set to GREEN Added comment: heterozygous variants cause dyskeratosis congenita Sources: Literature |
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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 v0.697 | RHOA |
Sue White gene: RHOA was added gene: RHOA was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: RHOA was set to Other Publications for gene: RHOA were set to 31570889 Phenotypes for gene: RHOA were set to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia Penetrance for gene: RHOA were set to Complete Review for gene: RHOA was set to GREEN gene: RHOA was marked as current diagnostic Added comment: mosaic heterozygous missense variants cause linear hypopigmentation, brain MRI changes with normal cognition, ocular and acral changes Sources: Literature |
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| Mendeliome v0.692 | PUS10 | Zornitza Stark Added comment: Comment when marking as ready: Agree, no evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.684 | TRIM28 |
Zornitza Stark gene: TRIM28 was added gene: TRIM28 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRIM28 were set to 30694527 Phenotypes for gene: TRIM28 were set to Wilm's tumour Review for gene: TRIM28 was set to GREEN Added comment: Eleven individuals with germline variants identified; plus one somatic. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development. Sources: Literature |
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| Mendeliome v0.681 | CBWD1 |
Zornitza Stark gene: CBWD1 was added gene: CBWD1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: CBWD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CBWD1 were set to 31862704 Phenotypes for gene: CBWD1 were set to CAKUT Review for gene: CBWD1 was set to RED Added comment: A pair of siblings with homozygous deletion in this gene reported; functional data including animal model. Sources: Literature |
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| Mendeliome v0.679 | DEF6 |
Zornitza Stark gene: DEF6 was added gene: DEF6 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: DEF6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DEF6 were set to 31308374 Phenotypes for gene: DEF6 were set to Systemic autoimmunity Review for gene: DEF6 was set to AMBER Added comment: Three individuals from two families, some functional data. Sources: Literature |
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| Mendeliome v0.678 | SLC2A8 | Zornitza Stark Added comment: Comment when marking as ready: Cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.677 | SETD5 | Zornitza Stark Added comment: Comment when marking as ready: PMID: 29484850: Review of all literature reporting SETD5 (table 1). Out of 42 patients described in these papers, 71.4% have motor impairment/delay, 69.0% speech impairment/delay, 23.8% eplilepsy/seizures, 38% congenital heart defects, 95.2% facial dysmorphism, 21.4% hand stereotypies/ritualised behaviour, 19% impaired vision, 42.8% muscle hypotonia and 28.6% polydactyly. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.668 | MRPS14 |
Zornitza Stark gene: MRPS14 was added gene: MRPS14 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: MRPS14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS14 were set to 30358850 Phenotypes for gene: MRPS14 were set to Combined oxidative phosphorylation deficiency 38, MIM# 618378 Review for gene: MRPS14 was set to RED Added comment: Single individual reported, functional data. 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 v0.652 | H3F3B | Zornitza Stark commented on gene: H3F3B: Elizabeth J Bhoj, H3F3A/B Consortium, Hakon H. Hakonarson.: Mutations In H3f3a And H3f3b Encoding Histone 3.3: Report Of 26 Patients With Neurodevelopmental And Congenital Manifestations. American Society of Human Genetics, Orlando, FL October 2017 Notes: Platform Presentation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.651 | H3F3A | Zornitza Stark commented on gene: H3F3A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.651 | KAT5 | Zornitza Stark Added comment: Comment when marking as ready: Cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.649 | ROBO4 |
Zornitza Stark gene: ROBO4 was added gene: ROBO4 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ROBO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ROBO4 were set to 30455415 Phenotypes for gene: ROBO4 were set to bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation Review for gene: ROBO4 was set to GREEN Added comment: Two families, functional data, incomplete penetrance. Sources: Literature |
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| Mendeliome v0.647 | MYMK |
Zornitza Stark gene: MYMK was added gene: MYMK was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYMK were set to 28681861 Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome; OMIM #254940 Review for gene: MYMK was set to GREEN Added comment: Sources: Expert list |
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| Mendeliome v0.646 | EDC3 |
Zornitza Stark gene: EDC3 was added gene: EDC3 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: EDC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EDC3 were set to 29685133; 25701870 Phenotypes for gene: EDC3 were set to Mental retardation, autosomal recessive 50, MIM# 616460 Review for gene: EDC3 was set to RED Added comment: Single family reported; some functional data. Sources: Expert list |
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| Mendeliome v0.644 | EIF3F |
Zornitza Stark gene: EIF3F was added gene: EIF3F was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EIF3F were set to 30409806 Phenotypes for gene: EIF3F were set to Mental retardation, autosomal recessive 67, MIM# 618295 Review for gene: EIF3F was set to GREEN Added comment: Nine individuals from 7 families reported, all homozygous for the same missense variant, p.(Phe232Val). This variant is present at 0.12% frequency in non-Finnish Europeans in gnomad (no homozygotes). 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 v0.635 | CXorf56 |
Zornitza Stark gene: CXorf56 was added gene: CXorf56 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: CXorf56 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: CXorf56 were set to 29374277 Phenotypes for gene: CXorf56 were set to Mental retardation, X-linked 107, MIM# 301013 Review for gene: CXorf56 was set to RED Added comment: Single multigenerational family reported. 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 v0.631 | KLHL15 |
Zornitza Stark gene: KLHL15 was added gene: KLHL15 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: KLHL15 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: KLHL15 were set to 25644381; 24817631 Phenotypes for gene: KLHL15 were set to Mental retardation, X-linked 103, MIM#300982 Review for gene: KLHL15 was set to AMBER Added comment: Two families described: variants maternally inherited in both, one deletion, the other truncating. Sources: Literature |
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| Mendeliome v0.629 | ODC1 |
Zornitza Stark gene: ODC1 was added gene: ODC1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ODC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ODC1 were set to 30475435 Phenotypes for gene: ODC1 were set to Intellectual disability; macrocephaly; dysmorphism Mode of pathogenicity for gene: ODC1 was set to Other Review for gene: ODC1 was set to GREEN Added comment: Four individuals with de novo GoF variants in this gene reported. Sources: Literature |
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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 v0.619 | UGP2 |
Zornitza Stark gene: UGP2 was added gene: UGP2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGP2 were set to 31820119 Phenotypes for gene: UGP2 were set to Epileptic encephalopathy; intellectual disability; microcephaly Review for gene: UGP2 was set to GREEN Added comment: 22 individuals from 15 families reported with the same homozygous missense variant in this gene, chr2:64083454A > G, which causes a disruption of the start codon in the shorter isoform, which is expressed in brain. Sources: Literature |
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| Mendeliome v0.618 | ADRA2B | Zornitza Stark Added comment: Comment when marking as ready: Comment when marking as ready: Association has in fact been REFUTED by Corbett et al 2019 (PMID:31664034, who identified an alternative cause in the original families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.595 | IFT74 |
Zornitza Stark gene: IFT74 was added gene: IFT74 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IFT74 were set to 27486776 Phenotypes for gene: IFT74 were set to Bardet-Biedl syndrome 20, MIM# 617119 Review for gene: IFT74 was set to AMBER Added comment: Single family and functional data. Sources: Expert list |
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| Mendeliome v0.594 | IFT81 | Zornitza Stark Added comment: Comment when marking as ready: Three families with skeletal dysplasia, one with nephronophthisis, one with eye phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.588 | PDE6D | Zornitza Stark Added comment: Comment when marking as ready: Second family identified in the literature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.565 | ADAM22 |
Zornitza Stark gene: ADAM22 was added gene: ADAM22 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAM22 were set to 27066583; 30237576 Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933 Review for gene: ADAM22 was set to AMBER Added comment: Two families reported; the second one as part of a large consanguineous cohort. 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 v0.561 | GABRB1 |
Zornitza Stark gene: GABRB1 was added gene: GABRB1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: GABRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRB1 were set to 23934111; 27273810; 31618474 Phenotypes for gene: GABRB1 were set to Epileptic encephalopathy, early infantile, 45, MIM# 617153 Review for gene: GABRB1 was set to GREEN Added comment: Three individuals reported, two as part of large epilepsy cohorts. Sources: Expert list |
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| Mendeliome v0.557 | GUF1 |
Zornitza Stark gene: GUF1 was added gene: GUF1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: GUF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GUF1 were set to 26486472 Phenotypes for gene: GUF1 were set to Epileptic encephalopathy, early infantile, 40, MIM# 617065 Review for gene: GUF1 was set to RED Added comment: Single family reported with homozygous missense in three sibs. 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 v0.540 | PPP1R12A | Zornitza Stark Added comment: Comment when marking as ready: Now published, 12 individuals, upgraded to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.534 | SPATC1L |
Zornitza Stark gene: SPATC1L was added gene: SPATC1L was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: SPATC1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPATC1L were set to 30177775 Phenotypes for gene: SPATC1L were set to Deafness Review for gene: SPATC1L was set to AMBER Added comment: Two families with compound het variants, and one family with heterozygous variant and dominant pattern of hearing loss described, some functional data. Sources: Expert list |
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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 v0.530 | TMEM132E |
Zornitza Stark gene: TMEM132E was added gene: TMEM132E was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: TMEM132E was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM132E were set to 25331638 Phenotypes for gene: TMEM132E were set to Deafness, autosomal recessive 99, MIM# 618481 Review for gene: TMEM132E was set to AMBER Added comment: Single family reported, supportive animal model. 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 v0.527 | SPNS2 |
Zornitza Stark gene: SPNS2 was added gene: SPNS2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: SPNS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPNS2 were set to 25356849 Phenotypes for gene: SPNS2 were set to Deafness, autosomal recessive 115, MIM# 618457 Review for gene: SPNS2 was set to AMBER Added comment: Single family reported, mouse model shows progressive hearing loss. Sources: Expert list |
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| Mendeliome v0.525 | ESRP1 |
Zornitza Stark gene: ESRP1 was added gene: ESRP1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: ESRP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESRP1 were set to 29107558 Phenotypes for gene: ESRP1 were set to Deafness, autosomal recessive 109, MIM# 618013 Review for gene: ESRP1 was set to AMBER Added comment: Single family with affected sibs, mouse model. 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 v0.517 | ROR1 |
Zornitza Stark gene: ROR1 was added gene: ROR1 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: ROR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ROR1 were set to 27162350 Phenotypes for gene: ROR1 were set to Deafness, autosomal recessive 108, MIM# 617654 Review for gene: ROR1 was set to AMBER Added comment: Single family, sibs with homozygous missense variant; mouse model. Sources: Expert list |
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| Mendeliome v0.515 | RIPOR2 |
Zornitza Stark gene: RIPOR2 was added gene: RIPOR2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: RIPOR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RIPOR2 were set to 24958875 Phenotypes for gene: RIPOR2 were set to Deafness, autosomal recessive 104, MIM# 616515 Review for gene: RIPOR2 was set to AMBER Added comment: Single family and animal model data. Sources: Expert list |
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| Mendeliome v0.511 | CLDN9 |
Zornitza Stark gene: CLDN9 was added gene: CLDN9 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: CLDN9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLDN9 were set to 31175426; 19696885 Phenotypes for gene: CLDN9 were set to Deafness, autosomal recessive Review for gene: CLDN9 was set to AMBER Added comment: Single family with multiple sibs reported; mouse model exhibits deafness. Sources: Literature |
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| Mendeliome v0.509 | TOP2B |
Zornitza Stark gene: TOP2B was added gene: TOP2B was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TOP2B were set to 31198993 Phenotypes for gene: TOP2B were set to Autosomal dominant deafness Review for gene: TOP2B was set to AMBER Added comment: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data. Sources: Literature |
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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 v0.471 | KITLG | Zornitza Stark Phenotypes for gene: KITLG were changed from to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.469 | KITLG | Zornitza Stark reviewed gene: KITLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 26522471; Phenotypes: Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.448 | CACNB4 | Zornitza Stark Added comment: Comment on phenotypes: One family with episodic ataxia; susceptibility locus for different types of epilepsy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.425 | FAT2 |
Zornitza Stark gene: FAT2 was added gene: FAT2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: FAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FAT2 were set to 29053796 Phenotypes for gene: FAT2 were set to Spinocerebellar ataxia 45, MIM#617769 Review for gene: FAT2 was set to AMBER Added comment: Segregates in one family, and identified in one apparently sporadic case. In vitro functional evidence. Sources: Expert list |
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| Mendeliome v0.423 | GDAP2 |
Zornitza Stark gene: GDAP2 was added gene: GDAP2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: GDAP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GDAP2 were set to 30084953 Phenotypes for gene: GDAP2 were set to Spinocerebellar ataxia, autosomal recessive 27, MIM#618369 Review for gene: GDAP2 was set to GREEN Added comment: Two families and animal model. 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 v0.414 | INSRR | Zornitza Stark Added comment: Comment on list classification: Agreed, cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.413 | GRIK5 | Zornitza Stark Added comment: Comment on list classification: Agreed, cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.388 | NUP37 |
Zornitza Stark gene: NUP37 was added gene: NUP37 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NUP37 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP37 were set to 30179222 Phenotypes for gene: NUP37 were set to Nephrotic syndrome Review for gene: NUP37 was set to RED Added comment: Single family reported with nephrotic syndrome. 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 v0.385 | NUP160 |
Zornitza Stark gene: NUP160 was added gene: NUP160 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NUP160 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP160 were set to 30179222 Phenotypes for gene: NUP160 were set to Nephrotic syndrome, type 19, MIM#618178 Review for gene: NUP160 was set to RED Added comment: Single family, no 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 v0.374 | KANK1 | Zornitza Stark Added comment: Comment on list classification: Amber for nephrotic after discussion with Chirag Patel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.372 | KANK4 |
Zornitza Stark gene: KANK4 was added gene: KANK4 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: KANK4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KANK4 were set to 25961457 Phenotypes for gene: KANK4 were set to Nephrotic syndrome Review for gene: KANK4 was set to AMBER Added comment: Two individuals from a single family reported; gene belongs to a family implicated in nephrotic syndrome. Sources: Expert list |
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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 v0.368 | PLS1 |
Zornitza Stark gene: PLS1 was added gene: PLS1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PLS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLS1 were set to 31397523; 31432506; 30872814 Phenotypes for gene: PLS1 were set to Deafness Review for gene: PLS1 was set to GREEN Added comment: Non-syndromic deafness in 5 families with mono allelic variants in this gene. Mouse model. 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 v0.365 | FST |
Zornitza Stark gene: FST was added gene: FST was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: FST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FST were set to 31215115 Phenotypes for gene: FST were set to Cleft lip and palate Review for gene: FST was set to RED Added comment: Single family reported. Sources: Literature |
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| Mendeliome v0.363 | GDF11 |
Zornitza Stark gene: GDF11 was added gene: GDF11 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: GDF11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GDF11 were set to 31215115 Phenotypes for gene: GDF11 were set to Cleft lip and palate Review for gene: GDF11 was set to AMBER Added comment: Cleft lip and palate, and rib and vertebral hypersegmentation in a single family. Mouse model. Sources: Literature |
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| Mendeliome v0.361 | PRDM13 |
Zornitza Stark gene: PRDM13 was added gene: PRDM13 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PRDM13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRDM13 were set to 30710461 Phenotypes for gene: PRDM13 were set to Retinal dystrophy Mode of pathogenicity for gene: PRDM13 was set to Other Review for gene: PRDM13 was set to GREEN Added comment: 8 individuals from three families reported with UPSTREAM NON-CODING variants in this gene. Sources: Literature |
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| Mendeliome v0.360 | MICB | Zornitza Stark Added comment: Comment when marking as ready: Agree, cannot find evidence for Mendelian gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.346 | SLC12A2 |
Zornitza Stark gene: SLC12A2 was added gene: SLC12A2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SLC12A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC12A2 were set to 30740830 Phenotypes for gene: SLC12A2 were set to Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation Review for gene: SLC12A2 was set to AMBER Added comment: Single individual with bi-alllelic deletion described; mouse model recapitulated the phenotype. Sources: Literature |
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| Mendeliome v0.344 | PANK4 |
Zornitza Stark gene: PANK4 was added gene: PANK4 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PANK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PANK4 were set to 30585370 Phenotypes for gene: PANK4 were set to Congenital posterior cataract Review for gene: PANK4 was set to AMBER Added comment: Variant segregated with cataract in single 4-generation family, functional data including mouse model. Sources: Literature |
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| Mendeliome v0.343 | CSNK1E |
Zornitza Stark gene: CSNK1E was added gene: CSNK1E was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: CSNK1E was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CSNK1E were set to 30488659 Phenotypes for gene: CSNK1E were set to Epileptic encephalopathy Review for gene: CSNK1E was set to RED Added comment: De novo splicing variant reported but in conjunction with STXBP1 variants; authors postulate it may contribute to susceptibility. Also reports linking variants in this gene to psychiatric disorders. Sources: Literature |
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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 v0.337 | POLD2 |
Zornitza Stark gene: POLD2 was added gene: POLD2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: POLD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLD2 were set to 31449058 Phenotypes for gene: POLD2 were set to Intellectual disability; immunodeficiency Review for gene: POLD2 was set to RED Added comment: Single family, functional data. Sources: Literature |
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| Mendeliome v0.335 | ZNF292 |
Zornitza Stark gene: ZNF292 was added gene: ZNF292 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ZNF292 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZNF292 were set to 31723249 Phenotypes for gene: ZNF292 were set to Intellectual disability; Autism; ADHD Review for gene: ZNF292 was set to GREEN Added comment: 28 families with spectrum of neurodevelopmental features (including ID, ASD, and ADHD) due to de novo ZNF292 variants (1 family inherited). No functional evidence of specific variants, but ZNF292 is highly expressed in the developing human brain. 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 v0.324 | TANC2 |
Zornitza Stark gene: TANC2 was added gene: TANC2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TANC2 were set to 31616000 Phenotypes for gene: TANC2 were set to Intellectual disability; autism; epilepsy; dysmorphism Review for gene: TANC2 was set to GREEN Added comment: 19 families with potentially disruptive heterozygous TANC2 variants, including 16 likely gene-disrupting mutations and three intragenic microdeletions. Patients presented with autism, intellectual disability, delayed language and motor development, epilepsy, facial dysmorphism, with complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. No functional evidence of specific variants, but they show TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, and shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes. 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 v0.320 | SOX4 |
Zornitza Stark gene: SOX4 was added gene: SOX4 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SOX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SOX4 were set to 30661772 Phenotypes for gene: SOX4 were set to Coffin-Siris syndrome 10; OMIM #618506 Review for gene: SOX4 was set to GREEN Added comment: 4 patients with syndromic DD/ID and de novo mutations in SOX4 gene. Functional assays demonstrated that the SOX4 proteins carrying these variants were unable to bind DNA in vitro and transactivate SOX reporter genes in cultured cells. 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 v0.309 | POU3F3 |
Zornitza Stark gene: POU3F3 was added gene: POU3F3 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: POU3F3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU3F3 were set to 24550763; 31303265 Phenotypes for gene: POU3F3 were set to Intellectual disability Review for gene: POU3F3 was set to GREEN Added comment: 19 individuals with DD/ID/speech issues and heterozygous POU3F3 disruptions, most of which were de novo variants. Positive functional cell-based analyses of pathogenic variants. 1 patient reported with whole gene deletion and ID. Sources: Literature |
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| Mendeliome v0.308 | PISD | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.297 | P4HTM |
Zornitza Stark gene: P4HTM was added gene: P4HTM was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: P4HTM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: P4HTM were set to 25078763; 30940925 Phenotypes for gene: P4HTM were set to Hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities; OMIM #618493 Review for gene: P4HTM was set to GREEN Added comment: 12 patients from 5 families with hypotonia, intellectual disability, and eye abnormalities, and homozygous or compound heterozygous pathogenic P4HTM gene variants. Segregated with the disorder in the families. In vitro functional expression studies of 3 of the P4HTM variants showed that they caused a significant decrease in the amount of soluble protein compared to wildtype. Sources: Literature |
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| Mendeliome v0.296 | NLGN1 |
Zornitza Stark gene: NLGN1 was added gene: NLGN1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: NLGN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NLGN1 were set to 30460678 Phenotypes for gene: NLGN1 were set to intellectual disability; autism Review for gene: NLGN1 was set to RED Added comment: homozygous variant in the NLGN1 gene found in a pair of monozygotic twin brothers with intellectual disability and autism. Segregated with disease. No functional studies. 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 v0.290 | MEPCE |
Zornitza Stark gene: MEPCE was added gene: MEPCE was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: MEPCE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MEPCE were set to 31467394 Phenotypes for gene: MEPCE were set to Intellectual disability; seizures Review for gene: MEPCE was set to RED Added comment: 1 patient with global DD and seizures with de novo MEPCE nonsense variant. mRNA and protein analyses identified nonsense-mediated mRNA decay to underlie the decreased amount of MEPCE in patient fibroblasts followed by LARP7 and 7SK snRNA downregulation and HEXIM1 upregulation. Flavopiridol treatment and ectopic MEPCE protein expression in patient fibroblasts rescued increased expression of six RNAP II-sensitive genes and suggested a possible repressive effect of MEPCE on P-TEFb-dependent transcription of specific genes. 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 v0.287 | MACROD2 |
Zornitza Stark gene: MACROD2 was added gene: MACROD2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: MACROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MACROD2 were set to 31055587 Phenotypes for gene: MACROD2 were set to intellectual disability; dysmorphic features; microcephaly Review for gene: MACROD2 was set to RED Added comment: 1 family with a few affected with microcephaly, ID, dysmorphic features, and polydactyly. Deletion of chromosome 20p12.1 involving the MACROD2 gene was found in several members of the family. qRT-PCR showed higher levels of a MACROD2 mRNA isoform in the individuals carrying the deletion. 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 v0.284 | LSM1 |
Zornitza Stark gene: LSM1 was added gene: LSM1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: LSM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSM1 were set to 31010896 Phenotypes for gene: LSM1 were set to intellectual disability; congenital abnormalities Review for gene: LSM1 was set to RED Added comment: 1 family with 2 siblings with global DD, multiple congenital anomalies, and abnormal eye movements, with homozygous splice variant in LSM1. Segregated with the phenotype in the family. Expression studies revealed absence of expression of the canonical isoform in the affected individuals. The Lsm1 knockout mice have a partially overlapping phenotype that affects the brain, heart, and eye. Sources: Literature |
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| Mendeliome v0.282 | LMAN2L |
Zornitza Stark gene: LMAN2L was added gene: LMAN2L was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: LMAN2L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: LMAN2L were set to 31020005; 26566883 Phenotypes for gene: LMAN2L were set to Mental retardation, autosomal recessive, 52; OMIM #616887 Review for gene: LMAN2L was set to AMBER Added comment: 1 consanguineous family with 7 individuals with ID and epilepsy, with homozygous LMAN2L missense mutation. Segregated with disease in family, and unaffected family members were heterozygous variant carriers. No functional studies. 1 non-consanguineous family with 4 affected with heterozygous frameshift LMAN2L mutation. Segregates in family. Mutation eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane. 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 v0.278 | ADGRG6 | Zornitza Stark Added comment: Comment when marking as ready: 1 family with 2 patients with profound ID, severe speech impairment, microcephaly, seizures, spasticity, and cerebellar hypoplasia, with homozygous missense variation in ADGRG6 (GPR126). No functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.271 | FRY |
Zornitza Stark gene: FRY was added gene: FRY was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: FRY was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FRY were set to 31487712; 27457812; 21937992 Phenotypes for gene: FRY were set to Intellectual disability Review for gene: FRY was set to AMBER Added comment: 1 patient with ID/DD and a novel homozygous deletion involving FRY gene identified by genomic SNP microarray. No functional evidence. 2 consanguineous families with 6 affected individuals with ID, and homozygous mutations of FRY. No functional evidence. 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 v0.268 | ETS1 |
Zornitza Stark gene: ETS1 was added gene: ETS1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ETS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ETS1 were set to 31160359 Phenotypes for gene: ETS1 were set to Intellectual disability Review for gene: ETS1 was set to RED Added comment: Single individual with de novo truncating variant in this gene; gene is Jacobsen syndrome critical region. Sources: Literature |
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| Mendeliome v0.267 | ELMOD1 |
Zornitza Stark gene: ELMOD1 was added gene: ELMOD1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ELMOD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ELMOD1 were set to 31327155 Phenotypes for gene: ELMOD1 were set to Intellectual disability Review for gene: ELMOD1 was set to RED Added comment: Single family reported. 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 v0.262 | DTYMK |
Zornitza Stark gene: DTYMK was added gene: DTYMK was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: DTYMK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DTYMK were set to 31271740 Phenotypes for gene: DTYMK were set to Intellectual disability; microcephaly Review for gene: DTYMK was set to RED Added comment: Single family, two affected sibs with compound het variants reported. Sources: Literature |
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| Mendeliome v0.261 | DNAJA1 |
Zornitza Stark gene: DNAJA1 was added gene: DNAJA1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: DNAJA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAJA1 were set to 30972502 Phenotypes for gene: DNAJA1 were set to Intellectual disability; seizures Review for gene: DNAJA1 was set to RED Added comment: Single family with multiple affected individuals reported with bi-allelic truncating variant in this gene. 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 v0.251 | CSDE1 |
Zornitza Stark gene: CSDE1 was added gene: CSDE1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: CSDE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CSDE1 were set to 31579823 Phenotypes for gene: CSDE1 were set to Autism; intellectual disability; seizures; macrocephaly Review for gene: CSDE1 was set to GREEN Added comment: 18 families reported with high impact (stoppage/frameshift) variants in this gene. Eight de novo, eight inherited, two with undetermined inheritance. Functional data. Parents who had the variants were also affected, though generally more mildly. Sources: Literature |
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| Mendeliome v0.250 | CNTN6 |
Zornitza Stark gene: CNTN6 was added gene: CNTN6 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: CNTN6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CNTN6 were set to 30836150; 28641109; 29983269 Phenotypes for gene: CNTN6 were set to Intellectual disability; autism; Tourette syndrome; schizophrenia Review for gene: CNTN6 was set to RED Added comment: Conflicting evidence based on CNV data, no SNVs identified. Sources: Literature |
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| Mendeliome v0.249 | CMAS |
Zornitza Stark gene: CMAS was added gene: CMAS was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: CMAS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CMAS were set to 31495922 Phenotypes for gene: CMAS were set to Intellectual disability Review for gene: CMAS was set to RED Added comment: Single family, no functional data. 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 v0.241 | PUS7 |
Zornitza Stark gene: PUS7 was added gene: PUS7 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PUS7 were set to 30526862; 30778726; 31583274 Phenotypes for gene: PUS7 were set to Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature; OMIM #618342 Review for gene: PUS7 was set to GREEN Added comment: 11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease. Sources: Literature |
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| Mendeliome v0.239 | SEMA5A |
Zornitza Stark gene: SEMA5A was added gene: SEMA5A was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SEMA5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEMA5A were set to 26395558 Phenotypes for gene: SEMA5A were set to Intellectual disability; autism Review for gene: SEMA5A was set to AMBER Added comment: 1 patient with de novo translocation t(5;22)(p15.3;q11.21) and ASD and ID. At the translocation breakpoint on chromosome 5, they observed a 861-kb deletion encompassing the end of the SEMA5A gene. No functional studies. 2 patients with ASD and predicted deleterious heterozygous variants (maternally inherited). No functional studies Sources: Literature |
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| Mendeliome v0.237 | SMARCC2 |
Zornitza Stark gene: SMARCC2 was added gene: SMARCC2 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SMARCC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCC2 were set to 30580808 Phenotypes for gene: SMARCC2 were set to Coffin-Siris syndrome 8; OMIM #618362 Review for gene: SMARCC2 was set to GREEN Added comment: 15 individuals with variable degrees of neurodevelopmental delay, growth retardation, prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features. Sources: Literature |
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| Mendeliome v0.235 | SMARCD1 |
Zornitza Stark gene: SMARCD1 was added gene: SMARCD1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SMARCD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCD1 were set to 30879640 Phenotypes for gene: SMARCD1 were set to Intellectual disability; dysmorphic features Review for gene: SMARCD1 was set to GREEN Added comment: 5 individuals with heterozygous SMARCD1 variants (4 de novo, 1 unk), and developmental delay, intellectual disability, hypotonia, feeding difficulties, dysmorphisms, and small hands and feet. 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 v0.222 | ALKBH8 |
Zornitza Stark gene: ALKBH8 was added gene: ALKBH8 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: ALKBH8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALKBH8 were set to 31079898 Phenotypes for gene: ALKBH8 were set to Intellectual developmental disorder, autosomal recessive 71, MIM#618504 Review for gene: ALKBH8 was set to GREEN Added comment: Two families and functional data. 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 v0.206 | OXR1 |
Zornitza Stark gene: OXR1 was added gene: OXR1 was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OXR1 were set to 31785787 Phenotypes for gene: OXR1 were set to Intellectual disability; seizures; cerebellar atrophy Review for gene: OXR1 was set to GREEN Added comment: Five individuals from three families. Sources: Literature |
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| Mendeliome v0.169 | CDK16 |
Zornitza Stark gene: CDK16 was added gene: CDK16 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: CDK16 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: CDK16 were set to 25644381 Phenotypes for gene: CDK16 were set to Intellectual disability Review for gene: CDK16 was set to AMBER Added comment: Single family described in this manuscript describing multiple candidate genes for XLID. Sources: Expert list |
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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 v0.147 | FBXO31 |
Zornitza Stark gene: FBXO31 was added gene: FBXO31 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: FBXO31 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FBXO31 were set to 24623383 Phenotypes for gene: FBXO31 were set to Mental retardation, autosomal recessive 45, MIM#615979 Review for gene: FBXO31 was set to RED Added comment: Single consanguineous family reported with homozygous truncating variant, limited functional evidence. Sources: Expert list |
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| Mendeliome v0.140 | ERMARD | Zornitza Stark Added comment: Comment when marking as ready: Single affected individual described in heterozygous missense in this gene; rest of evidence is based on cytogenetic data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.129 | DPP10 | Zornitza Stark edited their review of gene: DPP10: Added comment: Link to autism based on CNV data.; Changed publications: 28670437 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.61 | ADD3 |
Zornitza Stark gene: ADD3 was added gene: ADD3 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADD3 were set to 29768408; 23836506 Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3, MIM#617008 Added comment: Four families reported in the literature with bi-allelic variants in this gene causing intellectual disability. Sources: Expert list |
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| Mendeliome v0.53 | TTI1 | Sebastian Lunke Added comment: Comment on list classification: Some patient evidence for association with ID, no patients identified to support association with dystonia or ataxia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.43 | ZNF526 | Zornitza Stark Added comment: Comment on list classification: Found unpublished abstract linking to AR intellectual disability in consanguineous Iranian population, no functional data provided. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | MME |
Zornitza Stark gene: MME was added gene: MME was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: MME was set to Unknown |
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| Mendeliome v0.0 | AMMECR1 |
Zornitza Stark gene: AMMECR1 was added gene: AMMECR1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: AMMECR1 was set to Unknown |
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