ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1486C>T (p.Gln496Ter) (rs756250205)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219822 SCV000274009 pathogenic Hereditary cancer-predisposing syndrome 2017-10-20 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)
GeneDx RCV000483345 SCV000570526 pathogenic not provided 2017-08-04 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.1486C>T at the cDNA level and p.Gln496Ter (Q496X) 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 protein truncation. This variant has been reported in an individual with a personal history of ovarian cancer and melanoma (Seifert 2016) and is considered pathogenic.
Invitae RCV000469433 SCV000550528 pathogenic Familial cancer of breast 2019-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln496*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in the literature in an individual affected with melanoma and ovarian cancer (PMID: 27083775). ClinVar contains an entry for this variant (Variation ID: 230455). Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.