Submissions for variant NM_012463.4(ATP6V0A2):c.1430A>G (p.Asn477Ser)

dbSNP: rs532258057

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001113317	SCV001271080	uncertain significance	Cutis laxa with osteodystrophy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001760081	SCV001999846	uncertain significance	not provided	2019-12-13	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV001862889	SCV002190513	uncertain significance	ALG9 congenital disorder of glycosylation	2022-10-05	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 477 of the ATP6V0A2 protein (p.Asn477Ser). This variant is present in population databases (rs532258057, gnomAD 0.08%). 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: 883133). 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. 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.
Ambry Genetics	RCV003259099	SCV003953843	uncertain significance	Inborn genetic diseases	2023-04-27	criteria provided, single submitter	clinical testing	The c.1430A>G (p.N477S) alteration is located in exon 12 (coding exon 12) of the ATP6V0A2 gene. This alteration results from a A to G substitution at nucleotide position 1430, causing the asparagine (N) at amino acid position 477 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.