ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6653A>T (p.Asp2218Val)

dbSNP: rs2072561785
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001296043 SCV001484998 uncertain significance Hereditary breast ovarian cancer syndrome 2025-01-05 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 2218 of the BRCA2 protein (p.Asp2218Val). 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: 999974). 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.
GeneDx RCV001751561 SCV002006714 uncertain significance not provided 2019-12-24 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Also known as 6881A>T
Ambry Genetics RCV002366117 SCV002663829 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-04 criteria provided, single submitter clinical testing The p.D2218V variant (also known as c.6653A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 6653. The aspartic acid at codon 2218 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002366117 SCV003847339 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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