ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5655C>A (p.Cys1885Ter) (rs80358789)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220539 SCV000278194 pathogenic Hereditary cancer-predisposing syndrome 2015-09-04 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031566 SCV000146657 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000220539 SCV000905016 pathogenic Hereditary cancer-predisposing syndrome 2018-09-04 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031566 SCV000327255 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031566 SCV000300913 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000160093 SCV000210360 pathogenic not provided 2017-05-24 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.5655C>A at the cDNA level and p.Cys1885Ter (C1885X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 5883C>A. The substitution creates a nonsense variant, changing a Cysteine to a premature stop codon (TGC>TGA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not been previously reported the literature to our knowledge, it is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044709 SCV000916955 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-20 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5655C>A (p.Cys1885X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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 (eg. c.5656C>T, p.Gln1886X; c.5681dupA, p.Tyr1894X; c.5682C>G, p.Tyr1894X). The variant was absent in 30948 control chromosomes (gnomAD). The variant, c.5655C>A, has been reported in the literature in one individual affected with Hereditary Breast and Ovarian Cancer (Tung_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000044709 SCV000072722 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys1885*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant has been reported in an individual affected with breast cancer (PMID: 25186627). ClinVar contains an entry for this variant (Variation ID: 37985). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031566 SCV000296708 pathogenic Breast-ovarian cancer, familial 2 2015-03-18 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044709 SCV000587787 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031566 SCV000054171 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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