ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1456C>T (p.Gln486Ter) (rs80358434)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112924 SCV000300432 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000219957 SCV000275360 pathogenic Hereditary cancer-predisposing syndrome 2018-11-06 criteria provided, single submitter clinical testing The p.Q486* pathogenic mutation (also known as c.1456C>T), located in coding exon 9 of the BRCA2 gene, results from a C to T substitution at nucleotide position 1456. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This mutation has been identified in a family with hereditary breast and/or ovarian cancer from Norway (Heramb C et al. Hered Cancer Clin Pract 2018 Jan;16:3). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112924 SCV000326557 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000112924 SCV000605658 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
GeneDx RCV000520967 SCV000620196 pathogenic not provided 2017-08-17 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1456C>T at the cDNA level and p.Gln486Ter (Q486X) at the proteinlevel. Using alternate nomenclature this variant would be defined as BRCA2 1684C>T. The substitution creates anonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause lossof normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this varianthas not, to our knowledge, been reported in the literature, it is considered pathogenic
Counsyl RCV000112924 SCV000677669 likely pathogenic Breast-ovarian cancer, familial 2 2017-04-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000496375 SCV000694539 pathogenic Hereditary breast and ovarian cancer syndrome 2021-03-28 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1456C>T (p.Gln486X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 243790 control chromosomes. c.1456C>T has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories, a consotrium (CIMBA) and an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic (n=5)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000496375 SCV001586040 pathogenic Hereditary breast and ovarian cancer syndrome 2020-07-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln486*) 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 observed in several individuals affected with hereditary breast and ovarian cancer (PMID: 29339979, 29446198). ClinVar contains an entry for this variant (Variation ID: 51128). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000112924 SCV000145874 pathogenic Breast-ovarian cancer, familial 2 1999-06-22 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496375 SCV000587598 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.