ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5238dupT (p.Asn1747Terfs) (rs80359499)

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Total submissions: 17
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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) RCV000031535 SCV000300851 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 RCV000257922 SCV000072631 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1747*) 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: 11802209, 23110154, 16168118, 25682074, 26681312). This variant is also known as 5466insT in the literature. ClinVar contains an entry for this variant (Variation ID: 37954). 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 RCV000130726 SCV000185615 pathogenic Hereditary cancer-predisposing syndrome 2017-09-25 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 RCV000212240 SCV000210763 pathogenic not provided 2019-01-04 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.5238dupT at the cDNA level and p.Asn1747Ter (N1747X) at the protein level. The normal sequence with the base that is duplicated in brackets is TGTC[dupT]AACA. The duplication creates a nonsense variant, changing an Asparagine to a premature stop codon. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant, also reported as BRCA2 5466insT and 5237_5238insT using alternate nomenclature, has been reported in association with hereditary breast and/or ovarian cancer (Frank 1998, Meindl 2002, Nanda 2005, Pohlreich 2005, van der Hout 2006, Pern 2012, Song 2014, Wong-Brown 2015, Frey 2017) and is considered pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000257922 SCV000219349 pathogenic Hereditary breast and ovarian cancer syndrome 2015-11-06 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000031535 SCV000267778 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212240 SCV000296566 pathogenic not provided 2016-02-27 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031535 SCV000327184 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031535 SCV000488096 pathogenic Breast-ovarian cancer, familial 2 2015-12-28 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000257922 SCV000588099 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000257922 SCV000591954 pathogenic Hereditary breast and ovarian cancer syndrome 2015-09-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000257922 SCV000694848 pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-13 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5238dupT (p.Asn174X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 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. c.5241delC, c.5290_5291delTC, c.5303_5304delTT, c.5350_5351delAA, c.5351dupA). One in-silico tool predicts a damaging outcome for this variant. This variant of interest has been reported in multiple affected individuals via publications and is absent in 123290 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000130726 SCV000747811 pathogenic Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
Color RCV000130726 SCV000905014 pathogenic Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031535 SCV000054140 pathogenic Breast-ovarian cancer, familial 2 2011-05-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031535 SCV000146580 not provided Breast-ovarian cancer, familial 2 no assertion provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000257922 SCV000587753 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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