ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3103G>T (p.Glu1035Ter) (rs80358556)

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Total submissions: 14
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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) RCV000077292 SCV000282375 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 RCV000044119 SCV000072132 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1035*) 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 several individuals affected with breast and/or ovarian cancer (PMID: 17688236, 26681312, 26296701, 16912212), as well as an individual with glioblastoma (PMID: 26787237). ClinVar contains an entry for this variant (Variation ID: 51400). 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 RCV000131104 SCV000186034 pathogenic Hereditary cancer-predisposing syndrome 2018-01-15 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)
GeneDx RCV000212224 SCV000210304 pathogenic not provided 2018-11-21 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3103G>T at the cDNA level and p.Glu1035Ter (E1035X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as BRCA2 3331G>T using alternate nomenclature, has been observed in multiple individuals and families with Hereditary Breast and Ovarian Cancer syndrome (Ramus 2007, Ellingson 2015) and is considered pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212224 SCV000296718 pathogenic not provided 2015-11-28 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077292 SCV000326813 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077292 SCV000489204 pathogenic Breast-ovarian cancer, familial 2 2016-09-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000508209 SCV000602807 pathogenic not specified 2016-10-12 criteria provided, single submitter clinical testing
Color RCV000131104 SCV000683526 pathogenic Hereditary cancer-predisposing syndrome 2016-10-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044119 SCV000694667 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3103G>T (p.Glu1035X) variant (legacy name 3331G>T) 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. p.Gln1063X, p.Gln1129X, and p.Arg2520X). This variant is absent in 120800 control chromosomes from ExAC. This variant has been reported in several HBOC patients in literature (Malone_2006, Ramus_2007, Conner_2014, Tung_2015, Ellingson_2015, Susswein_2015, Meric-Bernstam_2016). In addition, several clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077292 SCV000109089 pathogenic Breast-ovarian cancer, familial 2 2013-12-03 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077292 SCV000146170 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044119 SCV000587656 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
True Health Diagnostics RCV000131104 SCV000787927 pathogenic Hereditary cancer-predisposing syndrome 2017-12-01 no assertion criteria provided clinical testing

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