ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1689G>A (p.Trp563Ter) (rs80358456)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA2) RCV000112960 SCV000145920 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000581281 SCV000688718 pathogenic Hereditary cancer-predisposing syndrome 2017-07-13 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112960 SCV000326591 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000112960 SCV000488684 likely pathogenic Breast-ovarian cancer, familial 2 2016-05-23 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112960 SCV000282358 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000043863 SCV000918840 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-23 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1689G>A (p.Trp563X) 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 (e.g., p.Leu579X and p.Lys585fsX3). The variant allele was found at a frequency of 4.1e-06 in 246026 control chromosomes. c.1689G>A has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000043863 SCV000071876 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 563 (p.Trp563*) of 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 an individual affected with cancer (PMID: 15131399), although the type was not specified. ClinVar contains an entry for this variant (Variation ID: 51175). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000043863 SCV000587604 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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