ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5864C>A (p.Ser1955Ter) (rs80358815)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000505916 SCV000602868 pathogenic not specified 2017-02-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162927 SCV000213414 pathogenic Hereditary cancer-predisposing syndrome 2017-08-02 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) RCV000077364 SCV000146718 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162927 SCV000903519 pathogenic Hereditary cancer-predisposing syndrome 2017-11-22 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077364 SCV000327303 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077364 SCV000220841 likely pathogenic Breast-ovarian cancer, familial 2 2014-10-28 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044777 SCV000592009 pathogenic Hereditary breast and ovarian cancer syndrome 2015-06-08 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000044777 SCV000588105 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077364 SCV000733275 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077364 SCV000282416 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735576 SCV000863714 pathogenic Breast and/or ovarian cancer 2014-10-13 no assertion criteria provided clinical testing
GeneDx RCV000221022 SCV000278865 pathogenic not provided 2018-04-20 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.5864C>A at the cDNA level and p.Ser1955Ter (S1955X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 6092C>A. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in breast, ovarian, and prostate cancer patients (Meindl 2002, Lubinski 2004, Cunningham 2014, Pritchard 2016, Barnes 2017). We consider this variant to be pathogenic.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077364 SCV000743314 pathogenic Breast-ovarian cancer, familial 2 2017-07-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044777 SCV000694908 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-22 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5864C>A (p.Ser1955X) 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.5909C>A/p.S1970X). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/124064 control chromosomes at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Variant was found to co-segregate in multiple HBOC families. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000044777 SCV000072790 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1955*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80358815, ExAC 0.002%). This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 11802209, 15131399, 16683254, 24504028, 24728189, 26586665), as well as prostate cancer and pancreatic cancer (PMID: 26483394, 27433846). This variant is also known as 6092C>A in the literature. ClinVar contains an entry for this variant (Variation ID: 51954). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000221022 SCV000778692 pathogenic not provided 2017-12-13 no assertion criteria provided clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077364 SCV000296595 pathogenic Breast-ovarian cancer, familial 2 2015-10-30 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044777 SCV000587807 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077364 SCV000109161 pathogenic Breast-ovarian cancer, familial 2 2012-07-06 no assertion criteria provided clinical testing

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