ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.74T>C (p.Val25Ala) (rs587780188)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000116029 SCV000149938 likely benign not specified 2017-10-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000233411 SCV000289703 uncertain significance Familial cancer of breast 2018-12-19 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 25 of the CHEK2 protein (p.Val25Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs587780188, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individuals affected with breast cancer, colon cancer, and ovarian, peritoneal, or fallopian tube cancer (PMID: 21244692, 29458332, 22006311). ClinVar contains an entry for this variant (Variation ID: 128085). Experimental studies have shown that this missense change is able to complement hypersensitivity to DNA damage to the level equivalent to wild-type CHEK2 in yeast assays (PMID: 22006311, 22419737). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000233411 SCV000489591 uncertain significance Familial cancer of breast 2016-10-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571943 SCV000665182 likely benign Hereditary cancer-predisposing syndrome 2018-04-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Intact protein function observed in appropriate functional assay(s)
Color RCV000571943 SCV000905157 likely benign Hereditary cancer-predisposing syndrome 2016-09-29 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.