ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2047T>C (p.Ser683Pro)

dbSNP: rs398122740
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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 RCV001854360 SCV002222105 uncertain significance Hereditary breast ovarian cancer syndrome 2021-09-29 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. 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. ClinVar contains an entry for this variant (Variation ID: 91769). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 21318380). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 683 of the BRCA2 protein (p.Ser683Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline.
Ambry Genetics RCV002415573 SCV002728153 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-22 criteria provided, single submitter clinical testing The p.S683P variant (also known as c.2047T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 2047. The serine at codon 683 is replaced by proline, an amino acid with similar properties. In one study, this variant was reported as a VUS in a HBOC family living in East Denmark (Hansen T et al. Familial Cancer. 2011; 10:207–212). This alteration has been previously reported and classified as variant of uncertain significance in the ClinVar database by the Sharing Clinical Reports Project (SCRP) (available from www.ncbi.nlm.nih.gov/clinvar/. Accessed 11/20/2015). This amino acid position is poorly 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 variant remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002415573 SCV003846473 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).
Sharing Clinical Reports Project (SCRP) RCV000077677 SCV000109480 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2006-01-30 no assertion criteria provided clinical testing

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