ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.616_617del (p.Val206fs) (rs1346554630)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564621 SCV000661701 pathogenic Hereditary cancer-predisposing syndrome 2017-05-18 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 RCV000564621 SCV000689707 pathogenic Hereditary cancer-predisposing syndrome 2016-12-16 criteria provided, single submitter clinical testing
GeneDx RCV000657297 SCV000779028 pathogenic not provided 2018-04-26 criteria provided, single submitter clinical testing This deletion of two nucleotides in CHEK2 is denoted c.616_617delGT at the cDNA level and p.Val206ArgfsX2 (V206RfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GACT[delGT]AGAT. The deletion causes a frameshift which changes a Valine to an Arginine at codon 206, and creates a premature stop codon at position 2 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000540422 SCV000633202 pathogenic Familial cancer of breast 2018-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val206Argfs*2) in the CHEK2 gene. It is expected to result 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 a CHEK2-related disease. 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.