ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1095+1G>A (rs768172525)

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 RCV000215927 SCV000275717 likely pathogenic Hereditary cancer-predisposing syndrome 2015-05-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting pathogenic classification
GeneDx RCV000520428 SCV000618481 likely pathogenic not provided 2017-05-16 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.1095+1G>A or IVS10+1G>A and consists of a G>A nucleotidesubstitution at the +1 position of intron 10 of the CHEK2 gene. This variant destroys a canonical splice donor site andis 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 has not, to our knowledge, been published inthe literature. Based on the currently available information, we consider CHEK2 c.1095+1G>A to be a likely pathogenicvariant.
Invitae RCV000468038 SCV000550422 likely pathogenic Familial cancer of breast 2018-06-21 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 10 of the CHEK2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs768172525, ExAC 0.002%). This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 231770). 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 RCV000520428 SCV000889323 likely pathogenic not provided 2018-05-03 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.