ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5040_5041TG[1] (p.Val1681fs) (rs80359478)

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Total submissions: 11
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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) RCV000031521 SCV000300819 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000044543 SCV000072556 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1681Glufs*7) 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 the literature in families affected with breast and/or ovarian cancer (PMID: 18489799, 22460208, 25366421, 22711857, 26843898). ClinVar contains an entry for this variant (Variation ID: 37940). 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 RCV000217031 SCV000276006 pathogenic Hereditary cancer-predisposing syndrome 2017-08-04 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 RCV000221298 SCV000278856 pathogenic not provided 2018-06-05 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.5042_5043delTG at the cDNA level and p.Val1681GlufsX7 (V1681EfsX7) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCTG[delTG]AGTC. The deletion causes a frameshift, which changes a Valine to a Glutamic Acid at codon 1681, and creates a premature stop codon at position 7 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.5042_5043delTG, previously reported as 5270delTG or 5270_5271delGT using alternate nomenclature, has been observed in association with breast and/or ovarian cancer (Machackova 2008, Beristain 2010, de Juan 2015, Ratajska 2015). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000221298 SCV000296599 pathogenic not provided 2015-10-14 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031521 SCV000327122 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000217031 SCV000683667 pathogenic Hereditary cancer-predisposing syndrome 2015-03-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044543 SCV000694823 pathogenic Hereditary breast and ovarian cancer syndrome 2016-02-26 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031521 SCV000054126 pathogenic Breast-ovarian cancer, familial 2 2011-08-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031521 SCV000146525 pathogenic Breast-ovarian cancer, familial 2 1999-06-22 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044543 SCV000587738 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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