ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8478C>A (p.Tyr2826Ter) (rs776353983)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
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) RCV000240987 SCV000301281 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 RCV000240987 SCV000489698 likely pathogenic Breast-ovarian cancer, familial 2 2016-11-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284444 SCV001470247 pathogenic not provided 2020-03-18 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.
Invitae RCV001388431 SCV001589420 pathogenic Hereditary breast and ovarian cancer syndrome 2020-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr2826*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs776353983, ExAC 0.006%). This variant has been observed in individual(s) with breast cancer (PMID: 28724667). ClinVar contains an entry for this variant (Variation ID: 254623). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001284444 SCV000592196 pathogenic not provided no assertion criteria provided clinical testing The BRCA2 p.Tyr2826X variant was not identified in the literature, nor was it identified in several database searches (dbSNP, NHLBI Exome Sequencing Project, HGMD, LOVD, COSMIC, ClinVar, GeneInsight COGR, BIC, UMD). The variant was identified in the Exome Aggregation Consortium (ExAC) database in 1 of 16542 chromosomes from a South Asian population. The p.Tyr2826X variant leads to a premature stop codon at position 2826, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.

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.