ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2755G>A (p.Glu919Lys) (rs431825298)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000082903 SCV001161611 benign Breast-ovarian cancer, familial 2 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 9.62E-06
Invitae RCV000231119 SCV000283193 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 919 of the BRCA2 protein (p.Glu919Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs431825298, ExAC 0.002%). This variant has been reported in several individuals with personal and/or family history of breast and ovarian cancer (PMID: 22366370, 30254663). ClinVar contains an entry for this variant (Variation ID: 96782). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their 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.
Ambry Genetics RCV000571395 SCV000668557 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-02 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000571395 SCV000906049 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985487 SCV001133724 uncertain significance not provided 2019-03-26 criteria provided, single submitter clinical testing
Mendelics RCV000082903 SCV001139040 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082903 SCV000114977 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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