ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6826C>A (p.Pro2276Thr)

dbSNP: rs80358907
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569837 SCV000665989 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-24 criteria provided, single submitter clinical testing The p.P2276T variant (also known as c.6826C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 6826. The proline at codon 2276 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is poorly conserved and threonine is a reference amino acid in several species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001298105 SCV001487149 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2276 of the BRCA2 protein (p.Pro2276Thr). This variant is present in population databases (rs80358907, gnomAD 0.006%). This missense change has been observed in individual(s) with BRCA2-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 52201). 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.
Fulgent Genetics, Fulgent Genetics RCV002496693 SCV002814785 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3 2022-04-08 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000569837 SCV003847485 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).
All of Us Research Program, National Institutes of Health RCV000113653 SCV004828481 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces proline with threonine at codon 2276 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has been identified in 1/250224 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV004721253 SCV005327627 uncertain significance not provided 2024-03-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 7054C>A
Breast Cancer Information Core (BIC) (BRCA2) RCV000113653 SCV000146946 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2010-09-18 no assertion criteria provided clinical testing

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