ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9253dupA (p.Thr3085Asnfs) (rs80359752)

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Total submissions: 21
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130780 SCV000185673 pathogenic Hereditary cancer-predisposing syndrome 2017-03-31 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) RCV000031808 SCV000147581 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000130780 SCV000292174 pathogenic Hereditary cancer-predisposing syndrome 2015-11-23 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031808 SCV000328084 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031808 SCV000220419 likely pathogenic Breast-ovarian cancer, familial 2 2014-06-16 criteria provided, single submitter literature only
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031808 SCV000744559 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031808 SCV000605645 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000195407 SCV000588127 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031808 SCV000733335 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031808 SCV000301365 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Fulgent Genetics,Fulgent Genetics RCV000031808 SCV000575733 pathogenic Breast-ovarian cancer, familial 2 2015-10-23 criteria provided, single submitter clinical testing
GeneDx RCV000045760 SCV000210800 pathogenic not provided 2018-12-26 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.9253dupA at the cDNA level and p.Thr3085AsnfsX26 (T3085NfsX26) at the protein level. The normal sequence, with the bases that are duplicated in braces, is GAAAAAA[A]CAGG. The duplication causes a frameshift, which changes a Threonine to an Asparagine at codon 3085, and creates a premature stop codon at position 26 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.9253dupA, also known as BRCA2 9481insA, 9481dupA and 9474insA using alternate nomenclature, has been observed in association with breast, ovarian and prostate cancer (Montagna 2002, Spearman 2008, Borg 2010, Kote-Jarai 2011, Kim 2012, Castro 2013, Kang 2015, Pal 2015). We consider this variant to be pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785231 SCV000923799 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Gharavi Laboratory,Columbia University RCV000045760 SCV000809461 pathogenic not provided 2018-09-16 no assertion criteria provided research
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000031808 SCV000839929 pathogenic Breast-ovarian cancer, familial 2 2018-04-27 criteria provided, single submitter clinical testing The c.9246_9247dupA (p.Thr3085Asnfs*26) frameshift variant in BRCA2 has been reported in multiple unrelated patients with breast, ovarian or prostate cancer [PMID 11389159, 16455195, 16683254, 21952622,22798144, 25330149]. Based on the current evidence, this variant is classified as pathogenic
Integrated Genetics/Laboratory Corporation of America RCV000195407 SCV000695224 pathogenic Hereditary breast and ovarian cancer syndrome 2016-11-02 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9253dupA (p.Thr3085Asnfs) 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.9294C>G/p.Tyr3098X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120176 control chromosomes. This variant has been reported in multiple Br/Ov cancer patients, with evidence of co-segregation of variant with disease. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000195407 SCV000073773 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr3085Asnfs*26) 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 particular variant has been reported in individuals and families affected with breast, ovarian, and prostate cancer (PMID: 11389159, 16455195, 16683254, 19656164, 21952622, 22798144, 23569316, 25330149). This variant is also known as 9474insA, 9481insA, 9253insA, and c.9253_9254insA in the literature. ClinVar contains an entry for this variant (Variation ID:38225). 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 RCV000031808 SCV000296685 pathogenic Breast-ovarian cancer, familial 2 2015-04-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045760 SCV000889181 pathogenic not provided 2015-04-15 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000195407 SCV000587992 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031808 SCV000054416 pathogenic Breast-ovarian cancer, familial 2 2012-12-11 no assertion criteria provided clinical testing

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