ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5768A>T (p.Asp1923Val)

dbSNP: rs45491005
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220914 SCV000279213 uncertain significance not provided 2019-09-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; Also known as BRCA2 5996A>T; This variant is associated with the following publications: (PMID: 23704879)
Ambry Genetics RCV001024502 SCV001186530 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-15 criteria provided, single submitter clinical testing The p.D1923V variant (also known as c.5768A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 5768. The aspartic acid at codon 1923 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854528 SCV002271743 uncertain significance Hereditary breast ovarian cancer syndrome 2023-07-18 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 aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1923 of the BRCA2 protein (p.Asp1923Val). This variant is present in population databases (rs45491005, gnomAD 0.007%). 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: 126079). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001024502 SCV003849090 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).
Breast Cancer Information Core (BIC) (BRCA2) RCV000113480 SCV000146693 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2003-12-23 no assertion criteria provided clinical testing

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