ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3703C>T (p.Gln1235Ter) (rs1555283366)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657710 SCV000779459 pathogenic not provided 2017-03-08 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3703C>T at the cDNA level and p.Gln1235Ter (Q1235X) 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781127 SCV000918975 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3703C>T (p.Gln1235X) 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.3744_3747delTGAG, p.Ser1248fsX10; c.3785C>A, p.Ser1262X; c.3847_3848delGT, p.Val1283fsX2). The variant was absent in 120326 control chromosomes. To our knowledge, no occurrence of c.3703C>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000781127 SCV001580569 pathogenic Hereditary breast and ovarian cancer syndrome 2020-09-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1235*) 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 not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 545990). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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