Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000599054 | SCV000339824 | pathogenic | not provided | 2016-02-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000599054 | SCV000709959 | pathogenic | not provided | 2025-02-11 | criteria provided, single submitter | clinical testing | Reported previously using alternate nomenclature, c.78_79insC, in an individual with cutis laxa and inguinal hernia who also harbored a ATP6V0A2 missense variant; however, parental studies were not performed to determine the phase of these two variants (PMID: 19321599); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed with a pathogenic variant on the opposite allele (in trans) in a patient with features consistent with ATP6V0A2-related cutis laxa spectrum referred for genetic testing at GeneDx; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19321599) |
| Labcorp Genetics |
RCV000689436 | SCV000817087 | pathogenic | ALG9 congenital disorder of glycosylation | 2024-10-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser27Glnfs*28) in the ATP6V0A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP6V0A2 are known to be pathogenic (PMID: 18157129, 19321599). This variant is present in population databases (rs745590426, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with autosomal recessive cutis laxa type 2 (PMID: 19321599). ClinVar contains an entry for this variant (Variation ID: 286400). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265727 | SCV002548464 | likely pathogenic | Cutis laxa | 2022-05-13 | criteria provided, single submitter | clinical testing | Variant summary: ATP6V0A2 c.78dupC (p.Ser27GlnfsX28) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2.1e-05 in 235348 control chromosomes. c.78dupC has been reported in the literature as c.78_79insC in a compound heterozygous genotype with a reportedly hypomorphic allele (c.260C>T, p.P87L) in at-least one individual with Cutis Laxa - ATP6V0A2 Related, who presented with mild systemic involvement (example, Hutchadowder_2009). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic with some citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005008254 | SCV005634171 | pathogenic | Cutis laxa with osteodystrophy; Wrinkly skin syndrome | 2024-04-16 | criteria provided, single submitter | clinical testing |