ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6212G>C (p.Ser2071Thr)

gnomAD frequency: 0.00001  dbSNP: rs80358861
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220310 SCV000273763 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-18 criteria provided, single submitter clinical testing The p.S2071T variant (also known as c.6212G>C), located in coding exon 10 of the BRCA2 gene, results from a G to C substitution at nucleotide position 6212. The serine at codon 2071 is replaced by threonine, an amino acid with similar properties. This variant was identified in 1 of 523 male breast cancer patients undergoing multigene panel testing (Rizzolo P et al. Int J Cancer, 2019 Jul;145:390-400). This variant was also identified in a cohort of 200 patients with a personal and/or family history suggestive of hereditary breast and ovarian cancer syndrome (Doddato G et al. Front Oncol, 2021 May;11:649435). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000532875 SCV000635496 uncertain significance Hereditary breast ovarian cancer syndrome 2024-11-16 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 2071 of the BRCA2 protein (p.Ser2071Thr). This variant is present in population databases (rs80358861, gnomAD 0.002%). This missense change has been observed in individual(s) with BRCA2-related conditions (PMID: 30613976, 34026625). ClinVar contains an entry for this variant (Variation ID: 230278). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Color Diagnostics, LLC DBA Color Health RCV000220310 SCV000688970 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-17 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000220310 SCV002536211 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-06 criteria provided, single submitter curation
University of Washington Department of Laboratory Medicine, University of Washington RCV000220310 SCV003852324 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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