ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8677C>T (p.Gln2893Ter) (rs397507409)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031760 SCV000327947 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) RCV000031760 SCV000301303 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 RCV000413575 SCV000490437 pathogenic not provided 2018-12-06 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8677C>T at the cDNA level and p.Gln2893Ter (Q2893X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA2 8905C>T using alternate nomenclature, has been reported in association with Hereditary Breast and Ovarian Cancer syndrome (Katagiri 1998, Laitman 2011, Takahashi 2017) and is considered pathogenic.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000031760 SCV000746274 likely pathogenic Breast-ovarian cancer, familial 2 2017-12-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045600 SCV000918831 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8677C>T (p.Gln2893X) 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 (eg. c.9196C>T/p.Gln3066X, c.9235delG/p.Val3079fsX4). The variant was absent in 120724 control chromosomes. c.8677C>T has been reported in the literature in individuals and at-least 1 family affected with Hereditary Breast and Ovarian Cancer where it was shown to co-segregate with disease. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000045600 SCV000073613 pathogenic Hereditary breast and ovarian cancer syndrome 2017-09-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2893*) 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 and families affected with breast cancer (PMID: 9609997, 26187060). ClinVar contains an entry for this variant (Variation ID: 38177). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031760 SCV000054368 pathogenic Breast-ovarian cancer, familial 2 2011-03-29 no assertion criteria provided clinical testing

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