Submissions for variant NM_012463.4(ATP6V0A2):c.309G>T (p.Lys103Asn)

gnomAD frequency: 0.00026  dbSNP: rs144499089

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000280712	SCV000376914	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	RCV000767074	SCV000534739	uncertain significance	not provided	2025-02-06	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Athena Diagnostics	RCV000439999	SCV000612471	uncertain significance	not specified	2017-04-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763801	SCV000894715	uncertain significance	Cutis laxa with osteodystrophy; Wrinkly skin syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001348420	SCV001542723	uncertain significance	ALG9 congenital disorder of glycosylation	2022-08-17	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 103 of the ATP6V0A2 protein (p.Lys103Asn). This variant is present in population databases (rs144499089, gnomAD 0.03%). 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: 307578). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Breakthrough Genomics, Breakthrough Genomics	RCV000767074	SCV005192044	uncertain significance	not provided		criteria provided, single submitter	not provided
Ambry Genetics	RCV004965395	SCV005519632	uncertain significance	Inborn genetic diseases	2024-08-19	criteria provided, single submitter	clinical testing	The c.309G>T (p.K103N) alteration is located in exon 4 (coding exon 4) of the ATP6V0A2 gene. This alteration results from a G to T substitution at nucleotide position 309, causing the lysine (K) at amino acid position 103 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.