ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8878C>T (p.Gln2960Ter) (rs80359140)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162940 SCV000213427 pathogenic Hereditary cancer-predisposing syndrome 2018-01-17 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) RCV000077455 SCV000147480 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162940 SCV000684004 pathogenic Hereditary cancer-predisposing syndrome 2017-04-25 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077455 SCV000327982 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077455 SCV000488176 pathogenic Breast-ovarian cancer, familial 2 2016-01-15 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000077455 SCV000605642 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077455 SCV000282462 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000223154 SCV000278883 pathogenic not provided 2018-10-05 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8878C>T at the cDNA level and p.Gln2960Ter (Q2960X) at the protein level. 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, also reported as BRCA2 9106C>T using alternate nomenclature, has been observed in individuals with early-onset, familial, and male breast cancer, as well as ovarian cancer (Santarosa 1999, Fruscalzo 2006, Miolo 2006, Manoukian 2007, Barber 2013, Safra 2013). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000045646 SCV000695185 pathogenic Hereditary breast and ovarian cancer syndrome 2017-05-05 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8878C>T (p.Gln2960X) 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.8902_8913delinsTCCC, p.Thr2968fsX47; c.8904delC, p.Val2969fsX7; c.8930delA, p.Tyr2977fsX11; c.8961_8964delGAGT, p.Ser2988fsX12). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120540 control chromosomes. This variant was reported in multiple individuals affected with HBOC with clear segregation with the disease (Aretini, 2003; Santarosa, 1999; Miolo, 2006) The vaiant is suspected to be a founder mutation in Italian population (Miolo, 2006). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000045646 SCV000073659 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 2960 (p.Gln2960*). 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 the literature in individuals and families with breast and/or ovarian cancer (PMID: 10449599, 24312913, 14531499, 18821011, 25863477, 26852130, 16764716). This variant is also known as 9106C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 52694). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000045646 SCV000838887 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000077455 SCV000196020 pathogenic Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000223154 SCV000600828 pathogenic not provided 2016-09-09 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045646 SCV000587974 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077455 SCV000109253 pathogenic Breast-ovarian cancer, familial 2 2007-01-08 no assertion criteria provided clinical testing

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