ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2589T>A (p.Asn863Lys) (rs80358521)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044020 SCV000072033 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130583 SCV000185455 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
GeneDx RCV000427575 SCV000512348 likely benign not specified 2017-07-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000427575 SCV000694613 likely benign not specified 2018-11-13 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.2589T>A (p.Asn863Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.8e-05 in 258438 control chromosomes, exclusively observed within the African subpopulation at a frequency of 0.00062 in the gnomAD database. This frequency is slightly lower than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (0.00062 vs. 0.00075). In addition, the variant was reported in 3 / 2559 African American women, who were older than 70 years of age, and never had cancer (in the FLOSSIES database). c.2589T>A has been also reported in the literature in an African American woman affected with breast cancer, however, this report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer (Pal 2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (two classifying it as likely benign, and one calling it a VUS). Based on the evidence outlined above, the variant was classified as likely benign.
Mendelics RCV000044020 SCV000838776 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000130583 SCV000903075 benign Hereditary cancer-predisposing syndrome 2016-04-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031375 SCV000053980 benign Breast-ovarian cancer, familial 2 2012-03-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031375 SCV000146076 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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