ClinVar Miner

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

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Total submissions: 8
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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 2020-10-05 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/or ovarian cancer (PMID: 22366370, 30254663). ClinVar contains an entry for this variant (Variation ID: 96782). Based on a multifactorial likelihood algorithm using genetic, in silico, and/or statistical data, this variant has been determined to have a low probability of being pathogenic (PMID: 31131967). 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 2020-08-28 criteria provided, single submitter clinical testing The p.E919K variant (also known as c.2755G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 2755. The glutamic acid at codon 919 is replaced by lysine, an amino acid with similar properties. One study detected this alteration in a cohort of 167 Croatian women with personal and/or family history of breast and/or ovarian cancer (Levanat S et al. Gene, 2012 May;498:169-76). This alteration has also been detected in 1/1045 Italian breast and/or ovarian cancer patients (Zuntini R et al. Front Genet, 2018 Sep;9:378). This amino acid position is not well conserved in available vertebrate 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.
Color Health, Inc 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 likely benign not provided 2020-09-04 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
Research and Development, ARUP Laboratories RCV001647071 SCV001854731 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
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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