ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6487C>T (p.Gln2163Ter) (rs398122559)

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Total submissions: 8
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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) RCV000076968 SCV000301057 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 RCV000483318 SCV000572278 pathogenic not provided 2016-11-11 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6487C>T at the cDNA level and p.Gln2163Ter (Q2163X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), 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.
Color Health, Inc RCV000579895 SCV000683788 pathogenic Hereditary cancer-predisposing syndrome 2017-03-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483318 SCV001133866 pathogenic not provided 2019-01-28 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Ambry Genetics RCV000579895 SCV001187487 pathogenic Hereditary cancer-predisposing syndrome 2019-10-08 criteria provided, single submitter clinical testing The p.Q2163* pathogenic mutation (also known as c.6487C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 6487. This changes the amino acid from a glutamine to a stop codon within coding exon 10. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192504 SCV001360688 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-04-04 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6487C>T (p.Gln2163X) 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 (e.g. c.6656C>G, p.Ser2219X; c.6952C>T, p.Arg2318X; c.7878G>A, p.Trp2626X). The variant was absent in 228928 control chromosomes (gnomAD). To our knowledge, no occurrence of c.6487C>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories 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. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001192504 SCV001375060 pathogenic Hereditary breast and ovarian cancer syndrome 2020-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2163*) 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). ClinVar contains an entry for this variant (Variation ID: 91451). 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) RCV000076968 SCV000108765 pathogenic Breast-ovarian cancer, familial 2 2011-07-06 no assertion criteria provided clinical testing

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