ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4978C>T (p.Pro1660Ser)

dbSNP: rs2137512328
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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 RCV001906742 SCV002184251 uncertain significance Hereditary breast ovarian cancer syndrome 2021-05-03 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 1660 of the BRCA2 protein (p.Pro1660Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 17503080). 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. 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 RCV002265045 SCV002547116 uncertain significance not provided 2022-01-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 5206C>T; This variant is associated with the following publications: (PMID: 17503080)
University of Washington Department of Laboratory Medicine, University of Washington RCV003156836 SCV003852255 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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