ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9380G>A (p.Trp3127Ter) (rs80359211)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131047 SCV000185977 pathogenic Hereditary cancer-predisposing syndrome 2018-01-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031818 SCV000147624 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031818 SCV000328119 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031818 SCV000301386 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000485069 SCV000567862 pathogenic not provided 2018-11-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.9380G>A at the cDNA level and p.Trp3127Ter (W3127X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 9608G>A . The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>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 Indian and Italian individuals with personal and/or family history of breast or ovarian cancer (Juwle 2012, Ricci 2014, Kwong 2016, Moran 2016), and it is considered pathogenic
Integrated Genetics/Laboratory Corporation of America RCV000781092 SCV000918910 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9380G>A (p.Trp3127X) 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.9382C>T (p.Arg3128X), c.9403delC (p.Leu3135fsX28), and c.9435_9436delGT (p.Ser3147fsX2)). The variant was absent in 277070 control chromosomes (gnomAD). The variant, c.9380G>A, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Juwle_2012, Moran_2017, Shah_2018, Tung_2014, Wang_2014). 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 ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031818 SCV000296586 pathogenic Breast-ovarian cancer, familial 2 2015-12-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031818 SCV000054426 pathogenic Breast-ovarian cancer, familial 2 2010-04-29 no assertion criteria provided clinical testing

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