ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6645C>G (p.Tyr2215Ter) (rs80358892)

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Total submissions: 6
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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) RCV000113621 SCV000301084 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113621 SCV000327486 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000657768 SCV000779521 pathogenic not provided 2018-04-12 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6645C>G at the cDNA level and p.Tyr2215Ter (Y2215X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Invitae RCV000690837 SCV000818566 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr2215*) 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 in the Leiden Open-source Variation Database (PMID: 21520333) and the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 126113). A different variant (c.6645_6648delCTCC) giving rise to the same protein effect observed here (p.Tyr2215*) has been reported in individuals affected with familial breast and ovarian cancer (PMID: 26848529, 26187060). 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) RCV000113621 SCV000146902 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Department of Pediatrics,Memorial Sloan Kettering Cancer Center RCV000490731 SCV000564128 pathogenic Familial cancer of breast 2016-11-25 no assertion criteria provided clinical testing

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