ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9082G>C (p.Ala3028Pro) (rs80359161)

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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 RCV000129295 SCV000184056 pathogenic Hereditary cancer-predisposing syndrome 2020-02-12 criteria provided, single submitter clinical testing The p.A3028P pathogenic mutation (also known as c.9082G>C), located in coding exon 22 of the BRCA2 gene, results from a G to C substitution at nucleotide position 9082. The alanine at codon 3028 is replaced by proline, an amino acid with highly similar properties. This alteration was found to segregate with disease in a family with early-onset breast cancer (Ambry internal data). This alteration was found to be deleterious in a cell-based homology-directed repair assay (Hart SN et al. Genet. Med., 2019 01;21:71-80). Internal structural analysis predicts that this alteration will disrupt single-stranded DNA binding (Ambry internal data). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758971 SCV000887956 uncertain significance not provided 2017-09-27 criteria provided, single submitter clinical testing
Invitae RCV001055261 SCV001219644 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 3028 of the BRCA2 protein (p.Ala3028Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 27273131). ClinVar contains an entry for this variant (Variation ID: 126199). This variant has been reported to affect BRCA2 protein function (PMID: 29884841). 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 Health, Inc RCV000129295 SCV001348397 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-11 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000114042 SCV000147530 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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