ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6559C>T (p.Pro2187Ser)

gnomAD frequency: 0.00001  dbSNP: rs868216475
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213792 SCV000279586 uncertain significance not provided 2022-12-28 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; Has not been previously published as pathogenic or benign to our knowledge; Also known as 6787C>T; This variant is associated with the following publications: (PMID: 32377563, 29884841, 31911673)
Color Diagnostics, LLC DBA Color Health RCV000773213 SCV000906805 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000822558 SCV000963367 uncertain significance Hereditary breast ovarian cancer syndrome 2022-05-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2187 of the BRCA2 protein (p.Pro2187Ser). 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: 234614). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%).
Ambry Genetics RCV000773213 SCV002665259 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-30 criteria provided, single submitter clinical testing The p.P2187S variant (also known as c.6559C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 6559. The proline at codon 2187 is replaced by serine, an amino acid with similar 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 RCV000773213 SCV003847270 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).
Fulgent Genetics, Fulgent Genetics RCV005008174 SCV005633955 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer 2024-02-29 criteria provided, single submitter clinical testing

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