ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6267_6269delinsC (p.Glu2089fs) (rs276174868)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129598 SCV000184382 pathogenic Hereditary cancer-predisposing syndrome 2017-07-20 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),Other strong data supporting pathogenic classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000031610 SCV000146805 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129598 SCV000903719 pathogenic Hereditary cancer-predisposing syndrome 2018-06-19 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031610 SCV000327375 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031610 SCV000301009 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 RCV000254646 SCV000210775 pathogenic not provided 2017-12-19 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.6267_6269delGCAinsC at the cDNA level and p.Glu2089AspfsX2 (E2089DfsX2) at the protein level. The surrounding sequence is CTGA[delGCA][insC]TAGT. The deletion and insertion causes a frameshift, which changes a Glutamic Acid to an Aspartic Acid at codon 2089, and creates a premature stop codon at position 2 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 6267_6269delGCAinsC, also known as 6495delGCAinsC and 6495del3insC using alternate nomenclature, has been reported in association with familial breast cancer, as well as male breast cancer (Vehmanen 1997, Kwiatkowska 2001, Wojcik 2016). We consider this variant to be pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785227 SCV000923795 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000464782 SCV000694951 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6267_6269delinsC (p.Glu2089Aspfs) 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.6270_6271delTA, p.His2090fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120114 control chromosomes and has been reported in affected individuals in the literature, including a male breast cancer patient and triple negative breast cancer patients (Kwiatkowska_2000, Wong-Brown_2015). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000464782 SCV000549815 pathogenic Hereditary breast and ovarian cancer syndrome 2016-11-13 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides and inserts 1 nucleotide in exon 11 of the BRCA2 mRNA (c.6267_6269delinsC), causing a frameshift at codon 2089. This creates a premature translational stop signal (p.Glu2089Aspfs*) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in several individuals affected with breast cancer (PMID: 9150152, 25682074, 26681312, 26843898, 26976419). This variant is also known as c.6495G>C, 6496delCA in the literature. ClinVar contains an entry for this variant (Variation ID: 38029). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000254646 SCV000600686 pathogenic not provided 2016-09-29 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031610 SCV000054217 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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