ClinVar Miner

Submissions for variant NM_012463.4(ATP6V0A2):c.515A>G (p.Lys172Arg) (rs142935490)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000422153 SCV000535619 uncertain significance not provided 2018-08-09 criteria provided, single submitter clinical testing The K172R variant of uncertain significance in the ATP6V0A2 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. K172R was not observed with any significant frequency in the NHLBI Exome Sequencing Project or in Exome Aggregation Consortium (ExAC), indicating it is not a common benign variant in these populations. The K172R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no pathogenic missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014), indicating that this region of the gene is not known to harbor disease-causing variants.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae RCV000797679 SCV000937252 uncertain significance ALG9 congenital disorder of glycosylation 2018-08-06 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 172 of the ATP6V0A2 protein (p.Lys172Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs142935490, ExAC 0.007%). This variant has not been reported in the literature in individuals with ATP6V0A2-related disease. ClinVar contains an entry for this variant (Variation ID: 392359). 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: "Tolerated"; PolyPhen-2: "Possibly 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.

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