ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5217_5223del (p.Thr1738_Tyr1739insTer) (rs80359496)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506286 SCV000602857 pathogenic not specified 2017-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131077 SCV000186007 pathogenic Hereditary cancer-predisposing syndrome 2018-02-19 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) RCV000077350 SCV000146571 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131077 SCV000292159 pathogenic Hereditary cancer-predisposing syndrome 2015-07-29 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077350 SCV000327177 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000077350 SCV000605664 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044613 SCV000591951 pathogenic Hereditary breast and ovarian cancer syndrome 2013-08-28 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077350 SCV000282401 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000219434 SCV000278858 pathogenic not provided 2019-01-07 criteria provided, single submitter clinical testing This deletion of seven nucleotides in BRCA2 is denoted c.5217_5223delTTTAAGT at the cDNA level and p.Tyr1739Ter (Y1739X) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CTTA[delTTTAAGT]AACA. This deletion creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAT>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as BRCA2 5445del7, has been reported in multiple Hereditary Breast and Ovarian Cancer syndrome families (Malone 2000, Scottish/Northern Irish BRCA1/BRCA2 Consortium 2003, H?berg-Vetti 2016). We consider this deletion to be pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000077350 SCV000839913 pathogenic Breast-ovarian cancer, familial 2 2018-04-27 criteria provided, single submitter clinical testing This c.5217_5223del (p.Tyr1739*) variant in exon 11 of the BRCA2 gene is a deletion of seven nucleotides and is predicted to cause loss of function of normal protein through mRNA decay or producing a truncated protein, which is a known disease mechanism for this gene. This particular variant (also published as c.5445del7) has been reported in multiple hereditary breast and ovarian cancer patients (PMID: 10717622, 26350514). The c.5217_5223del variant in the BRCA2 gene is classified as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044613 SCV000694844 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-19 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5217_5223delTTTAAGT (p.Tyr1739X) 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. This variant was found in 1/121342 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multiple publications have cited the variant in affected individulas, along with multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000044613 SCV000072626 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1739*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80359496, ExAC 0.002%). This variant has been reported in individuals affected with breast cancer and ovarian cancer (PMID: 10717622, 26350514). This variant is also known as 5445del7 in the literature. ClinVar contains an entry for this variant (Variation ID: 51822). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000219434 SCV000296636 pathogenic not provided 2015-08-12 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044613 SCV000587750 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077350 SCV000109147 pathogenic Breast-ovarian cancer, familial 2 2013-03-06 no assertion criteria provided clinical testing

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