ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9249A>T (p.Lys3083Asn) (rs80359191)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131342 SCV000186317 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000114073 SCV000147579 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Color RCV000131342 SCV000906962 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-15 criteria provided, single submitter clinical testing
Counsyl RCV000114073 SCV000487894 uncertain significance Breast-ovarian cancer, familial 2 2015-12-04 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000212287 SCV000592265 uncertain significance not specified 2013-11-08 criteria provided, single submitter clinical testing
GeneDx RCV000759688 SCV000210499 uncertain significance not provided 2018-05-10 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9249A>T at the cDNA level, p.Lys3083Asn (K3083N) at the protein level, and results in the change of a Lysine to an Asparagine (AAA>AAT). This variant has been observed in at least one individual with epithelial ovarian cancer and one individual with prostate cancer (Cunningham 2014, Maier 2014). BRCA2 Lys3083Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Yang 2000). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Lys3083Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000045758 SCV000073771 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-03-22 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 3083 of the BRCA2 protein (p.Lys3083Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs80359191, ExAC 0.003%). This variant has been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033), and in individuals affected with prostate cancer or ovarian cancer (PMID: 25111659, 24504028). ClinVar contains an entry for this variant (Variation ID: 52784). An algorithm developed specifically for the BRCA2 gene suggests that this missense change is likely to be tolerated (PMID: 19043619). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759688 SCV000889179 uncertain significance not provided 2017-11-24 criteria provided, single submitter clinical testing

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