ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9403del (p.Leu3135fs) (rs80359760)

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Total submissions: 16
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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) RCV000077470 SCV000282473 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000045813 SCV000073826 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu3135Phefs*28) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant has been reported in individuals and families affected with breast and/or ovarian cancer (PMID: 22160602, 18489799, 15024741, 15146557, 21203900). This variant is also known as 9630delC and 9631delC in the literature. ClinVar contains an entry for this variant (Variation ID: 52831). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000164828 SCV000215511 pathogenic Hereditary cancer-predisposing syndrome 2017-11-24 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077470 SCV000296640 pathogenic Breast-ovarian cancer, familial 2 2015-08-04 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077470 SCV000328126 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077470 SCV000488275 pathogenic Breast-ovarian cancer, familial 2 2016-02-16 criteria provided, single submitter clinical testing
GeneDx RCV000414565 SCV000490441 pathogenic not provided 2017-12-07 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.9403delC at the cDNA level and p.Leu3135PhefsX28 (L3135FfsX28) at the protein level. The normal sequence, with the base that is deleted in brackets, is AGGC[delC]TTCT. The deletion causes a frameshift which changes a Leucine to a Phenylalanine at codon 3135, and creates a premature stop codon at position 28 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.9403delC, previously reported as 9631delC and 9630delC, has been reported in several families with a reported history consistent with Hereditary Breast and Ovarian Cancer syndrome (Foretova 2004, Gorski 2004, Machackova 2008, Konecny 2011, Schneegans 2012). We consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045813 SCV000592284 pathogenic Hereditary breast and ovarian cancer syndrome 2013-02-22 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000077470 SCV000605681 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045813 SCV000695237 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-04 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9403delC (p.Leu3135Phefs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 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 (e.g.c.9331G>T/p.Glu3111X, c.9403delC/p.Leu3135fs). One in silico tool predicts a damaging outcome for this variant. This variant has been reported in numerous HBOC patients and is absent in 121310 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077470 SCV000744564 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Color RCV000164828 SCV000903965 pathogenic Hereditary cancer-predisposing syndrome 2017-12-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077470 SCV000109268 pathogenic Breast-ovarian cancer, familial 2 2012-07-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077470 SCV000147631 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 RCV000045813 SCV000588004 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077470 SCV000733338 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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