ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1459C>T (p.Gln487Ter) (rs876659250)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214536 SCV000275496 pathogenic Hereditary cancer-predisposing syndrome 2015-05-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion)
GeneDx RCV000657722 SCV000779472 pathogenic not provided 2017-06-05 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.1459C>T at the cDNA level and p.Gln487Ter (Q487X) 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. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Invitae RCV000699485 SCV000828198 pathogenic Familial cancer of breast 2018-08-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln487*) in the CHEK2 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 CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 231595). Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.

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