ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7463G>A (p.Arg2488Lys) (rs80358968)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000168600 SCV000210650 likely benign not specified 2017-11-16 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.
Counsyl RCV000077401 SCV000488203 uncertain significance Breast-ovarian cancer, familial 2 2016-01-22 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000077401 SCV000575726 uncertain significance Breast-ovarian cancer, familial 2 2015-08-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563199 SCV000661177 likely benign Hereditary cancer-predisposing syndrome 2017-04-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with mutation in same gene (phase unknown),Other data supporting benign classification
Color RCV000563199 SCV000689049 likely benign Hereditary cancer-predisposing syndrome 2017-03-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588937 SCV000695069 likely benign not provided 2017-02-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7463G>A (p.Arg2488Lys) variant located in the helical domain (via InterPro) involves the alteration of a conserved nucleotide, which 3/5 in silico tools predict a damaging outcome. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/120914, which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA2 variant, 1/1333. Multiple publications cite the variant in affected individuals, although with limited information (ie, lack of co-occurrence data), however, Claes_2004, does indicate that the variant did not segregate with disease for one of the affected families. Multiple clinical diagnostic laboratories/databases cite the variant with conflicting classifications, likely benign/neutral [3x] and uncertain significance [3x]). In addition, one database, BRCAshare indicates the variant had been identified in 17 individuals, which 6 carried another potentially pathogenic BRCA variant: BRCA2: c.2745_2746delTT (p.Val917LysfsX18) and BRCA1: 1 - c.1961dup (p.Tyr655ValfsX18), 1 - c.4183C>T (p.Gln1395X), 1 - c.IVS21+1G>T (c.5332+1G>T), 1 - c.4389C>A (p.Tyr1463X), and c.442_4357del (p.Glu149TyrfsX2). Therefore, suggesting the variant to be likely benign. Although the variant is not located in an commonly known location to affect splicing (ie, within +/- 2 bp of an exon/intron junction), two publications found the variant to not affect splicing via functional studies. Therefore, taking all lines of evidence into consideration, the variant of interest has been classified as likely benign.
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077401 SCV000744518 uncertain significance Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Mendelics RCV000077401 SCV001139180 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077401 SCV000109198 likely benign Breast-ovarian cancer, familial 2 2012-11-29 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077401 SCV000147095 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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