ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5261A>T (p.Asp1754Val)

dbSNP: rs772772727
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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 RCV001963335 SCV002241608 uncertain significance Hereditary breast ovarian cancer syndrome 2024-03-05 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 1754 of the BRCA2 protein (p.Asp1754Val). 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: 1460546). 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 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003156904 SCV003847123 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).
Ambry Genetics RCV003156904 SCV005027895 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-14 criteria provided, single submitter clinical testing The p.D1754V variant (also known as c.5261A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 5261. The aspartic acid at codon 1754 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, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004774564 SCV005385024 uncertain significance not provided 2024-02-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 5489A>T

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