ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6462_6463TC[3] (p.Gln2157fs) (rs80359596)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131035 SCV000185965 pathogenic Hereditary cancer-predisposing syndrome 2017-06-12 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) RCV000031629 SCV000146867 not provided Breast-ovarian cancer, familial 2 no assertion provided clinical testing
Center for Studies on Hereditary Cancer,University of Bologna RCV000771024 SCV000902520 pathogenic Colorectal cancer no assertion criteria provided research
Color RCV000131035 SCV000683785 pathogenic Hereditary cancer-predisposing syndrome 2017-03-20 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031629 SCV000327437 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044965 SCV000592056 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031629 SCV000282426 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Fulgent Genetics,Fulgent Genetics RCV000031629 SCV000575754 pathogenic Breast-ovarian cancer, familial 2 2016-01-29 criteria provided, single submitter clinical testing
GeneDx RCV000160302 SCV000210781 pathogenic not provided 2018-04-04 criteria provided, single submitter clinical testing This deletion of 2 nucleotides is denoted BRCA2 c.6468_6469delTC at the cDNA level and p.Gln2157IlefsX18 (Q2157IfsX18) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCTC[delTC]AATT. The deletion causes a frameshift, which changes a Glutamine to an Isoleucine at codon 2157, and creates a premature stop codon at position 18 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 6468_6469delTC, previously reported as 6696delTC using alternate nomenclature, has been reported in association with Hereditary Breast and Ovarian Cancer and has been published as a common pathogenic variant among individuals of Italian ancestry (Ottini 2000, Ottini 2003, Manoukian 2007, Veschi 2007, Papi 2009, Arai 2017). We consider this variant to be pathogenic.
GeneKor MSA RCV000160302 SCV000296828 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785368 SCV000923939 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000044965 SCV000694976 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-02 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6468_6469delTC (p.Gln2157Ilefs) 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. The variant was not observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in numerous affected individuals in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000044965 SCV000072978 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2157Ilefs*18) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast, ovarian and uterine cancer (PMID: 8988179, 21989927, 23096105, 17591842, 17513806). In the literature, this variant is also known as 6690delTC and 6696delTC. ClinVar contains an entry for this variant (Variation ID: 38047). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000044965 SCV000605800 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-15 criteria provided, single submitter clinical testing The p.Gln2157fs variant in BRCA2 has been reported in >30 individuals with BRCA2 -associated cancers (Vietri 2012, Ghiorzo 2012, Manoukian 2007, Gao 2000, Veschi 2009, Papi 2007, Breast Cancer Information Core (BIC) database) and was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 2157 and le ads to a premature termination codon 18 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in individuals w ith hereditary breast and ovarian cancer (HBOC). In addition, this variant was c lassified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000282426.1). In summary, this variant meets criteria to be cl assified as pathogenic for HBOC in an autosomal dominant manner based upon the p redicted impact to the protein.
Mendelics RCV000044965 SCV000838840 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160302 SCV000887882 pathogenic not provided 2016-06-24 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044965 SCV000587851 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031629 SCV000054236 pathogenic Breast-ovarian cancer, familial 2 2012-08-27 no assertion criteria provided clinical testing

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