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| Intellectual disability - microarray and sequencing v4.53 | ATP6V0A1 |
Arina Puzriakova Tag Q3_22_rating was removed from gene: ATP6V0A1. Tag Q3_22_NHS_review was removed from gene: ATP6V0A1. |
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| Intellectual disability - microarray and sequencing v4.53 | ATP6V0A1 | Arina Puzriakova reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v4.52 | ATP6V0A1 |
Arina Puzriakova Source NHS GMS was added to ATP6V0A1. Source Expert Review Green was added to ATP6V0A1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v3.1742 | ATP6V0A1 | Eleanor Williams changed review comment from: Removed the Q3_22_MOI tag as the MOI has been proposed to be Monoallelic by all.; to: Removed the Q3_22_MOI tag as the MOI has been proposed to be Monoallelic by all reviewers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1742 | ATP6V0A1 | Eleanor Williams commented on gene: ATP6V0A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1742 | ATP6V0A1 | Eleanor Williams Tag Q3_22_MOI was removed from gene: ATP6V0A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1614 | ATP6V0A1 | Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen https://www.ebi.ac.uk/gene2phenotype/gfd?dbID=4422 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1614 | ATP6V0A1 | Sarah Leigh Phenotypes for gene: ATP6V0A1 were changed from ATP6V0A1-related developmental disorder (monoallelic) to ATP6V0A1-related developmental disorder (monoallelic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1613 | ATP6V0A1 | Sarah Leigh Phenotypes for gene: ATP6V0A1 were changed from Developmental disorder; Rett syndrome-like to ATP6V0A1-related developmental disorder (monoallelic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1612 | ATP6V0A1 | Sarah Leigh Tag Q3_22_MOI tag was added to gene: ATP6V0A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1612 | ATP6V0A1 | Sarah Leigh edited their review of gene: ATP6V0A1: Added comment: Not associated with a phenotype in OMIM, but as definitive Gen2Phen gene for ATP6V0A1-related developmental disorder (monoallelic). At least four variants have been reported as de novo heterozygous variants in 14 apparently unrelated cases, with intellectual disability (11/11 cases who could be assessed), epilepsy/EEG abnormalities (11/13 who could be assessed), microcephaly (6/12 cases who could be assessed), ataxia (6/13 cases who could be assessed) and various other phenotypic features (PMID: 34909687 (table 1) & 33833240). Six additional ATP6V0A1 variants were reported as biallelic in four apparently unrelated cases, who all had intellectual disability, epilepsy/EEG abnormalities plus cerebral and cerebellar atrophy / brain atrophy (PMID: 34909687 (table 1) & 33833240).; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1612 | ATP6V0A1 | Sarah Leigh changed review comment from: Comment on mode of inheritance: Monallelic mode of inheritance has been selected for ATP6V0A1, although four families showed biallelic ATP6V0A1 variants. This in line Gen2Phen and the views Zornitza Stark and Mike Spiller who have reviewed this gene, and reflects the inconstitancies of the phenotypes amongst these individuals. As more data is obtained, it maybe that the mode of inheritance is changed to both mono and biallelic.; to: Comment on mode of inheritance: Monoallelic mode of inheritance has been selected for ATP6V0A1, although four families showed biallelic ATP6V0A1 variants. This in line Gen2Phen and the views Zornitza Stark and Mike Spiller who have reviewed this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1612 | ATP6V0A1 | Sarah Leigh Publications for gene: ATP6V0A1 were set to 30842224; 33057194; 34909687 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1611 | ATP6V0A1 | Sarah Leigh changed review comment from: Comment on mode of inheritance: Monallelic mode of inheritance has been selected for ATP6V0A1, although four families showed biallelic ATP6V0A1 variants. This in line the views Zornitza Stark and Mike Spiller who have reviewed this gene, and reflects the inconstitancies of the phenotypes amongst these individuals. As more data is obtained, it maybe that the mode of inheritance is changed to both mono and biallelic.; to: Comment on mode of inheritance: Monallelic mode of inheritance has been selected for ATP6V0A1, although four families showed biallelic ATP6V0A1 variants. This in line Gen2Phen and the views Zornitza Stark and Mike Spiller who have reviewed this gene, and reflects the inconstitancies of the phenotypes amongst these individuals. As more data is obtained, it maybe that the mode of inheritance is changed to both mono and biallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1611 | ATP6V0A1 | Sarah Leigh Added comment: Comment on mode of inheritance: Monallelic mode of inheritance has been selected for ATP6V0A1, although four families showed biallelic ATP6V0A1 variants. This in line the views Zornitza Stark and Mike Spiller who have reviewed this gene, and reflects the inconstitancies of the phenotypes amongst these individuals. As more data is obtained, it maybe that the mode of inheritance is changed to both mono and biallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1611 | ATP6V0A1 | Sarah Leigh Mode of inheritance for gene: ATP6V0A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1610 | ATP6V0A1 | Sarah Leigh Classified gene: ATP6V0A1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1610 | ATP6V0A1 | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1610 | ATP6V0A1 | Sarah Leigh Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1609 | ATP6V0A1 |
Sarah Leigh Tag Q3_22_rating tag was added to gene: ATP6V0A1. Tag Q3_22_NHS_review tag was added to gene: ATP6V0A1. |
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| Intellectual disability - microarray and sequencing v3.1609 | ATP6V0A1 | Sarah Leigh Publications for gene: ATP6V0A1 were set to 30842224; 33057194 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1606 | ATP6V0A1 |
Mike Spiller changed review comment from: Bott et al 2021 PMID: 34909687 17 individuals from 14 unrelated families 12 individuals with de novo variants in ATP6V0A1. Associated with severe intellectual disability and refractory seizures following initial normal development. 1 stillborn; other 11 all have intellectual disability and slowing of developmental progression. 10 have epilepsy, microcephaly also common and MRI abnormalities in some. Dysmorphic features less common. 7/12 have recurrent hotspot variant NM_001130021.3 c.2219G>A R740Q. Biallelic inheritance also suggested - 2 separate families (apparently unrelated by IBD analysis) with affected individuals compound heterozygous for c.445delG p.(Glu149fs) and c.1483C>T p.(Arg495Trp). Phenotype of ID, epilepsy, but with ataxia and cerebellar anomalies. Gene involved in proton transport into organelles. Cell lines stably expressing R740Q show reduced endolysosome acidification consistent with reduced transporter function. Supported by data showing impaired maturation of Cathepsin D (requires acidic pH). Also refer to studies of yeast homologue showing that R735 (corresponds to human R740) is essential for proton transport function (Kawasaki-Nishi et al 2001 PMID: 11592980). Strong evidence that pathogenic missense variants in this gene cause severe ID/epilepsy, Less certain for biallelic inheritance. Recommend upgrade to Green for ID and epilepsy.; to: Bott et al 2021 PMID: 34909687 17 individuals from 14 unrelated families 12 individuals with de novo variants in ATP6V0A1. Associated with severe intellectual disability and refractory seizures following initial normal development. 1 stillborn; other 11 all have intellectual disability and slowing of developmental progression. 10 have epilepsy, microcephaly also common and MRI abnormalities in some. Dysmorphic features less common. 7/12 have recurrent hotspot variant NM_001130021.3 c.2219G>A R740Q. Biallelic inheritance also suggested - 2 separate families (apparently unrelated by IBD analysis) with affected individuals compound heterozygous for c.445delG p.(Glu149fs) and c.1483C>T p.(Arg495Trp). Phenotype of ID, epilepsy, but with ataxia and cerebellar anomalies. Gene involved in proton transport into organelles. Cell lines stably expressing R740Q show reduced endolysosome acidification consistent with reduced transporter function. Supported by data showing impaired maturation of Cathepsin D (requires acidic pH). Also refer to studies of yeast homologue showing that R735 (corresponds to human R740) is essential for proton transport function (Kawasaki-Nishi et al 2001 PMID: 11592980). Strong evidence that heterozygous pathogenic missense variants in this gene cause severe ID/epilepsy, Less certain for biallelic inheritance. Recommend upgrade to Green for ID and epilepsy. |
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| Intellectual disability - microarray and sequencing v3.1606 | ATP6V0A1 | Mike Spiller reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34909687; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.579 | ATP6V0A1 | Ivone Leong Classified gene: ATP6V0A1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.579 | ATP6V0A1 | Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is not enough evidence to support a gene-disease association so this gene has been given an Amber rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.579 | ATP6V0A1 | Ivone Leong Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.510 | ATP6V0A1 |
Zornitza Stark gene: ATP6V0A1 was added gene: ATP6V0A1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP6V0A1 were set to 30842224; 33057194 Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like Review for gene: ATP6V0A1 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating). PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype Sources: Literature |
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