ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5286_5287TC[2] (p.Ser1764fs) (rs80359503)

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Total submissions: 12
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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) RCV000031537 SCV000300857 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 RCV000044629 SCV000072642 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1764Lysfs*3) 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 observed in the literature in individuals with a personal and/or family history of breast and/or ovarian cancers (PMID: 11972384, 23479189, 24504028). ClinVar contains an entry for this variant (Variation ID: 37956). 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 RCV000215243 SCV000274228 pathogenic Hereditary cancer-predisposing syndrome 2017-08-07 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031537 SCV000327194 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031537 SCV000488636 pathogenic Breast-ovarian cancer, familial 2 2016-05-12 criteria provided, single submitter clinical testing
GeneDx RCV000481345 SCV000566976 pathogenic not provided 2018-01-16 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.5290_5291delTC at the cDNA level and p.Ser1764LysfsX3 (S1764KfsX3) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCTC[delTC]AAAAAAT. The deletion causes a frameshift, which changes a Serine to a Lysine at codon 1764, and creates a premature stop codon at position 3 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.5290_5291delTC, also published as 5518delTC and 5514delTC using alternate nomenclature, has been reported in association with Hereditary Breast and Ovarian Cancer (Reedy 2002, Kauff 2003, Lubinski 2004, Song 2014). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481345 SCV000600637 pathogenic not provided 2017-05-10 criteria provided, single submitter clinical testing
Color RCV000215243 SCV000688926 pathogenic Hereditary cancer-predisposing syndrome 2017-07-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044629 SCV000694855 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-29 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5290_5291delTC (p.Ser1764LysfsX3) 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.5614A>T/p.Lys1872X, c.5624delA/p.Lys1875fsX34). The variant was absent in 247964 control chromosomes. c.5290_5291delTC has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Reedy_2002, Cunningham_2014, Jimenez_2013, Lubinski_2004, Li_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight 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.
Sharing Clinical Reports Project (SCRP) RCV000031537 SCV000054142 pathogenic Breast-ovarian cancer, familial 2 2011-09-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031537 SCV000146592 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 RCV000044629 SCV000587758 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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