ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7126G>A (p.Ala2376Thr)

dbSNP: rs730881552
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001992227 SCV002282497 uncertain significance Hereditary breast ovarian cancer syndrome 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2376 of the BRCA2 protein (p.Ala2376Thr). This variant is present in population databases (rs730881552, gnomAD 0.003%). 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: 1497117). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004999598 SCV005625271 uncertain significance not provided 2024-10-27 criteria provided, single submitter clinical testing The BRCA2 c.7126G>A (p.Ala2376Thr) variant has been identified in the published literature in reportedly healthy individuals (PMID: 30287823 (2018), 36243179 (2022)). The frequency of this variant in the general population, 0.000004 (1/251160 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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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