ClinVar Miner

Submissions for variant NM_012463.4(ATP6V0A2):c.309G>T (p.Lys103Asn) (rs144499089)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,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 2018-06-21 criteria provided, single submitter clinical testing The K103N variant of uncertain significance in the ATP6V0A2 gene has not been published as a pathogenic or benign variant to our knowledge. This variant was not observed with any significant frequency in either approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or the Exome Aggregation Consortium. Although this substitution occurs at a position where amino acids with similar properties to Lysine are tolerated across species, K103N is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, in silico analysis predicts K103N is probably damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with ARCL2A (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Athena Diagnostics Inc 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
Invitae RCV001348420 SCV001542723 uncertain significance ALG9 congenital disorder of glycosylation 2020-02-20 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 103 of the ATP6V0A2 protein (p.Lys103Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs144499089, ExAC 0.02%). This variant has not been reported in the literature in individuals 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: Tolerated; 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.

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