ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5158dupT (p.Ser1720Phefs) (rs80359489)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129981 SCV000184805 pathogenic Hereditary cancer-predisposing syndrome 2016-06-06 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000077744 SCV000146550 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000129981 SCV000683676 pathogenic Hereditary cancer-predisposing syndrome 2016-12-22 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077744 SCV000327143 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044569 SCV000591945 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077744 SCV000300834 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 RCV000486941 SCV000564785 pathogenic not provided 2017-08-23 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.5158dupT at the cDNA level and p.Ser1720PhefsX7 (S1720FfsX7) at the protein level. The normal sequence, with the base that is duplicated in braces, is TAAT[T]CAAA. The duplication causes a frameshift which changes a Serine to a Phenylalanine at codon 1720, 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.5158dupT, previously reported as c.5386dupT or c.5386insT using alternate nomenclature, has been observed in multiple patients with a personal and/or family history of breast and/or ovarian cancer (Zhang 2011, Coppa 2014, Finch 2015). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044569 SCV000916919 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-30 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5158dupT (p.Ser1720PhefsX7) 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.5217_5223delTTTAAGT/p.Tyr1739X, c.5238dupT/p.Asn1747X). The variant was absent in 228900 control chromosomes. c.5158dupT has been reported in the literature in individuals affected with Hereditary Breast and/or Ovarian Cancer. 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. Seven 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 RCV000044569 SCV000072582 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1720Phefs*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 individuals affected with breast and/or ovarian cancer (PMID: 21324516, 25395318, 26219728). This variant is also known as c.5158_5159insT and 5386insT in the literature. ClinVar contains an entry for this variant (Variation ID: 51781). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000044569 SCV000838807 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000486941 SCV000600627 pathogenic not provided 2016-08-31 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044569 SCV000587748 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077744 SCV000109547 pathogenic Breast-ovarian cancer, familial 2 2012-07-12 no assertion criteria provided clinical testing

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