ClinVar Miner

Submissions for variant NM_012463.4(ATP6V0A2):c.1457C>T (p.Ser486Leu)

gnomAD frequency: 0.00009  dbSNP: rs201271558
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000418070 SCV000533088 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ATP6V0A2 gene. The S486L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S486L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with ATP6V0A2-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant
Invitae RCV001851065 SCV002300550 uncertain significance ALG9 congenital disorder of glycosylation 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 486 of the ATP6V0A2 protein (p.Ser486Leu). This variant is present in population databases (rs201271558, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATP6V0A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 390297). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP6V0A2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV000418070 SCV003834446 uncertain significance not provided 2021-01-28 criteria provided, single submitter clinical testing

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