Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413672 | SCV000492139 | uncertain significance | not specified | 2016-12-06 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ATP6V0A2 gene. The N749S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N749S variant 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. Additionally, 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. However, it is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Invitae | RCV001850997 | SCV002112162 | uncertain significance | ALG9 congenital disorder of glycosylation | 2021-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 749 of the ATP6V0A2 protein (p.Asn749Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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"). This variant has not been reported in the literature in individuals with ATP6V0A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 373538). This variant is not present in population databases (ExAC no frequency). |