ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.743C>T (p.Ala248Val)

dbSNP: rs276174893
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000692746 SCV000820586 uncertain significance Hereditary breast ovarian cancer syndrome 2023-03-13 criteria provided, single submitter clinical testing 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. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 248 of the BRCA2 protein (p.Ala248Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 571569). 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 BRCA2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.
Baylor Genetics RCV003459689 SCV004216049 uncertain significance Familial cancer of breast 2023-07-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478418 SCV004220557 uncertain significance not provided 2023-01-27 criteria provided, single submitter clinical testing It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). The variant has not been reported in individuals with BRCA2-related disease in the published literature. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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