ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5959C>T (p.Gln1987Ter) (rs80358828)

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Total submissions: 9
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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) RCV000113510 SCV000300956 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000434288 SCV000296644 pathogenic not provided 2015-07-25 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113510 SCV000327315 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000434288 SCV000515786 pathogenic not provided 2017-03-28 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.5959C>T at the cDNA level and p.Gln1987Ter (Q1987X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 6187C>T. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual referred for BRCA1/2 genetic testing (Zanella 2017), and is considered pathogenic.
Ambry Genetics RCV000567880 SCV000665940 pathogenic Hereditary cancer-predisposing syndrome 2017-11-24 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000567880 SCV000683744 pathogenic Hereditary cancer-predisposing syndrome 2017-06-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496769 SCV000916871 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-29 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5959C>T (p.Gln1987X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 120624 control chromosomes. c.5959C>T has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (see e.g. Azzollini 2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113510 SCV000146739 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496769 SCV000587814 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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