ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.683+1G>T (rs786203650)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167053 SCV000217880 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Color RCV000167053 SCV000913592 likely pathogenic Hereditary cancer-predisposing syndrome 2018-07-21 criteria provided, single submitter clinical testing
Counsyl RCV000204794 SCV000488795 likely pathogenic Familial cancer of breast 2016-06-21 criteria provided, single submitter clinical testing
GeneDx RCV000216702 SCV000279478 likely pathogenic not provided 2018-08-03 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.683+1G>T or IVS5+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 5 of the CHEK2 gene. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant was observed in three individuals who underwent multi-gene panel testing; however specific personal and family history of cancer were not provided (Leedom 2016). Based on currently available evidence, we consider CHEK2 c.683+1G>T to be a likely pathogenic variant.
Invitae RCV000204794 SCV000259449 likely pathogenic Familial cancer of breast 2018-12-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the CHEK2 gene. It is expected to disrupt RNA splicing and likely results 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: 187334). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000216702 SCV000888119 pathogenic not provided 2017-11-15 criteria provided, single submitter clinical testing

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.