ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.409C>T (p.Arg137Ter) (rs730881701)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160452 SCV000274055 pathogenic Hereditary cancer-predisposing syndrome 2017-09-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000160452 SCV000903769 pathogenic Hereditary cancer-predisposing syndrome 2016-09-27 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763477 SCV000894259 pathogenic Familial cancer of breast; Li-Fraumeni syndrome 2; Osteosarcoma; Malignant tumor of prostate 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000254656 SCV000211017 pathogenic not provided 2018-10-23 criteria provided, single submitter clinical testing This pathogenic variant is denoted CHEK2 c.409C>T at the cDNA level and p.Arg137Ter (R137X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least two individuals with breast cancer as well as in three individuals who underwent multi-gene panel testing for hereditary cancer (Leedom 2016, Sun 2017). We consider CHEK2 Arg137Ter to be pathogenic.
Invitae RCV000229303 SCV000289685 pathogenic Familial cancer of breast 2018-10-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg137*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs730881701, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with breast cancer (PMID: 28724667), and who underwent genetic tests for the risk of hereditary cancer, including breast cancer (PMID: 27751358). ClinVar contains an entry for this variant (Variation ID: 182452). 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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