ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5130_5133del (p.Asp1709_Tyr1710insTer) (rs80359484)

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Total submissions: 15
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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) RCV000077345 SCV000282399 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000044563 SCV000072576 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1710*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs760558178, ExAC 0.01%). This variant has been reported in multiple individuals affected with breast cancer (PMID: 9012404, 23479189, 19656415, 25682074, 26586665, 26845104). This variant is also known as 5358del4 and p.Tyr1693X in the literature. ClinVar contains an entry for this variant (Variation ID: 51775). 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 RCV000131075 SCV000186005 pathogenic Hereditary cancer-predisposing syndrome 2017-05-24 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)
University of Washington Department of Laboratory Medicine,University of Washington RCV000210164 SCV000266042 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing
GeneDx RCV000215028 SCV000278857 pathogenic not provided 2018-08-09 criteria provided, single submitter clinical testing This deletion of 4 nucleotides is denoted BRCA2 c.5130_5133delTGTA at the cDNA level and p.Tyr1710Ter (Y1710X) at the protein level. This deletion is also known as BRCA2 5358_5361delTGTA, 5358delTGTA, or 5358del4 using alternate nomenclature. The normal sequence, with the bases that are deleted in brackets, is ATTA[TGTA]GGAA. The deletion creates a nonsense variant, which changes a Tyrosine to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.5130_5133delTGTA has been reported in men and women with a personal history of breast cancer as well as in other individuals meeting HBOC testing criteria (Friedman 1997, Thomassen 2008, Fackenthal 2012, Wong-Brown 2015, Kwong 2016). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000215028 SCV000296722 pathogenic not provided 2015-02-20 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077345 SCV000327138 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077345 SCV000488360 pathogenic Breast-ovarian cancer, familial 2 2016-03-08 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000044563 SCV000588097 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Color RCV000131075 SCV000683672 pathogenic Hereditary cancer-predisposing syndrome 2016-09-14 criteria provided, single submitter clinical testing
GeneKor MSA RCV000215028 SCV000693569 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044563 SCV000917012 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-06 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5130_5133delTGTA (p.Tyr1710X) 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. The variant allele was found at a frequency of 4.5e-06 in 222984 control chromosomes. c.5130_5133delTGTA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Friedman 1997, Ramus 2007, Thomassen 2008, Soumittra 2009, Fackenthal 2012). 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. 11 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) RCV000077345 SCV000109142 pathogenic Breast-ovarian cancer, familial 2 2010-09-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077345 SCV000146544 pathogenic Breast-ovarian cancer, familial 2 2014-01-07 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044563 SCV000587747 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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