ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6373dup (p.Thr2125fs) (rs80359577)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164585 SCV000215244 pathogenic Hereditary cancer-predisposing syndrome 2018-04-13 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) RCV000031623 SCV000146834 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031623 SCV000327407 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031623 SCV000605647 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031623 SCV000301025 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 RCV000044926 SCV000210778 pathogenic not provided 2017-04-25 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.6373dupA at the cDNA level and p.Thr2125AsnfsX4 (T2125NfsX4) at the protein level. The normal sequence, with the base that is duplicated in brackets, is GAAAAA[dupA]CCTG. The duplication causes a frameshift which changes a Threonine to an Asparagine at codon 2125, and creates a premature stop codon at position 4 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.6373dupA, previously reported as 6601insA and 6602insA using alternate nomenclature, has been reported in association with breast, ovarian, and pancreatic cancer (Risch 2001, Meindl 2002, Zhang 2011, Zhen 2015). We consider this variant to be pathogenic.
Invitae RCV000203626 SCV000072939 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr2125Asnfs*4) 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, ovarian and pancreatic cancer (PMID: 11179017, 11802209, 26681312, 26483394). It is also known as 6601insA or 6602insA in the literature. ClinVar contains an entry for this variant (Variation ID: 38041). 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 RCV000044926 SCV000600698 pathogenic not provided 2017-07-25 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000203626 SCV000587838 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031623 SCV000054230 pathogenic Breast-ovarian cancer, familial 2 2012-03-07 no assertion criteria provided clinical testing

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