ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3158T>G (p.Leu1053Ter) (rs41293477)

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Total submissions: 11
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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) RCV000031401 SCV000282377 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000162916 SCV000213403 pathogenic Hereditary cancer-predisposing syndrome 2018-01-24 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031401 SCV000326818 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031401 SCV000489489 pathogenic Breast-ovarian cancer, familial 2 2016-10-11 criteria provided, single submitter clinical testing
GeneDx RCV000424640 SCV000517371 pathogenic not provided 2015-06-01 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.3158T>G at the cDNA level and p.Leu1053Ter (L1053X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TGA), 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 a patient with early onset prostate cancer and is considered pathogenic (Kote-Jarai 2011).
Department of Medical Genetics,Oslo University Hospital RCV000031401 SCV000605657 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Color RCV000162916 SCV000683528 pathogenic Hereditary cancer-predisposing syndrome 2017-03-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496393 SCV000917039 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3158T>G (p.Leu1053X) 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.3166C>T, p.Gln1056X; c.3170_3174delAGAAA, p.Lys1057fsX8; c.3187C>T, p.Gln1063X). The variant was absent in 241474 control chromosomes (gnomAD). The variant, c.3158T>G, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Lubinski_2004, Mitra_2009). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven 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.
Sharing Clinical Reports Project (SCRP) RCV000031401 SCV000054006 pathogenic Breast-ovarian cancer, familial 2 2011-05-31 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031401 SCV000146179 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 RCV000496393 SCV000587658 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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