ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8680C>T (p.Gln2894Ter) (rs397508002)

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Total submissions: 6
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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) RCV000661884 SCV000784210 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Color RCV000581796 SCV000689145 pathogenic Hereditary cancer-predisposing syndrome 2016-11-21 criteria provided, single submitter clinical testing
GeneKor MSA RCV000585644 SCV000693590 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000585644 SCV000779379 pathogenic not provided 2016-09-19 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8680C>T at the cDNA level and p.Gln2894Ter (Q2894X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 8908C>T. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), 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 association with familial and early-onset breast cancer and is considered pathogenic (Purnomosari 2007, Negura 2010).
Integrated Genetics/Laboratory Corporation of America RCV000781156 SCV000919029 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-16 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8680C>T (p.Gln2894X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.8695C>T (p.Gln2899X), c.8777T>A (p.Leu2926X), c.8878C>T (p.Gln2960X)). The variant was absent in 246142 control chromosomes. c.8680C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Eniu_2017, Negura_2017, Negura_2011, Negura_2010, Purnomosari_2007). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four 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.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577659 SCV000679003 not provided Familial cancer of breast no assertion provided literature only

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