ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8067T>A (p.Cys2689Ter) (rs80359046)

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Total submissions: 11
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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) RCV000113864 SCV000301240 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Counsyl RCV000113864 SCV000220678 likely pathogenic Breast-ovarian cancer, familial 2 2014-09-09 criteria provided, single submitter literature only
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113864 SCV000327812 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000416520 SCV000494293 pathogenic Hereditary breast and ovarian cancer syndrome 2015-01-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571445 SCV000673071 pathogenic Hereditary cancer-predisposing syndrome 2016-02-15 criteria provided, single submitter clinical testing The p.C2689* pathogenic mutation (also known as c.8067T>A), located in coding exon 17 of the BRCA2 gene, results from a T to A substitution at nucleotide position 8067. This changes the amino acid from a cysteine to a stop codon within coding exon 17. This variant has been reported in studies of patients with suspected hereditary breast and/or ovarian cancer and in a patient with Fanconi anemia (Stratton M et al. Lancet 1997 May; 349(9064):1505-10; Peelen T et al. Br. J. Cancer 2000 Jan; 82(1):151-6.;Litton JK et al. Cancer 2012 Jan; 118(2):321-5; Bayraktar S et al. Cancer 2012 Mar; 118(6):1515-22; Ameziane N et al. Anemia 2012; 2012:132856; Vos JR et al. Cancer Epidemiol. Biomarkers Prev. 2014 Nov; 23(11):2482-91). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008; 10:294).
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000113864 SCV000743340 pathogenic Breast-ovarian cancer, familial 2 2014-10-08 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000113864 SCV000744531 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
GeneDx RCV000657589 SCV000779326 pathogenic not provided 2016-07-19 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8067T>A at the cDNA level and p.Cys2689Ter (C2689X) at the protein level. The substitution creates a nonsense variant, which changes a Cysteine to a premature stop codon (TGT>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Using alternate nomenclature, this variant would be defined as BRCA2 8295T>A and has been reported in multiple individuals with personal and family histories consistent with hereditary breast cancer (Breast Cancer Linkage Consortium 1997, Litton 2000, Peelen 2000, van der Hout 2006, Bayraktar 2012). We consider this variant to be pathogenic.
Mendelics RCV000416520 SCV000838866 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113864 SCV000147263 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000113864 SCV000733312 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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