ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.85C>T (p.Gln29Ter) (rs761494650)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167444 SCV000218300 pathogenic Hereditary cancer-predisposing syndrome 2018-01-04 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 RCV000167444 SCV000292166 pathogenic Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Counsyl RCV000228262 SCV000677821 likely pathogenic Familial cancer of breast 2016-12-23 criteria provided, single submitter clinical testing
GeneDx RCV000485654 SCV000568938 likely pathogenic not provided 2018-07-17 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.85C>T at the cDNA level and p.Gln29Ter (Q29X) 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. This variant has been reported in at least one individual with prostate cancer (Mandelker 2017). It is considered likely pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785428 SCV000924000 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000228262 SCV000289713 pathogenic Familial cancer of breast 2018-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln29*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs761494650, ExAC 0.002%). This nonsense change has been observed in an individual with breast cancer (PMID: 28008555). ClinVar contains an entry for this variant (Variation ID: 187694). 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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