ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.319+2T>A (rs587782401)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131434 SCV000186416 likely pathogenic Hereditary cancer-predisposing syndrome 2018-03-21 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 RCV000131434 SCV000684628 likely pathogenic Hereditary cancer-predisposing syndrome 2018-05-08 criteria provided, single submitter clinical testing
Counsyl RCV000545158 SCV000785922 likely pathogenic Familial cancer of breast 2018-01-10 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515447 SCV000611186 likely pathogenic Familial cancer of breast; Li-Fraumeni syndrome 2; Osteosarcoma; Malignant tumor of prostate 2017-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000212411 SCV000211009 likely pathogenic not provided 2018-08-02 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.319+2T>A or IVS2+2T>A and consists of a T>A nucleotide substitution at the +2 position of intron 2 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 has been observed in an individual with early-onset or familial breast cancer, another with thyroid and bilateral breast cancer, and at least one other with a microsatellite-stable colorectal cancer (Mantere 2017, Rohlin 2017, Dominguez-Valentin 2018). Based on the currently available information, we consider CHEK2 c.319+2T>A to be a likely pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000131434 SCV000698793 likely pathogenic Hereditary cancer-predisposing syndrome 2017-07-03 criteria provided, single submitter clinical testing Variant summary: The CHEK2 c.319+2T>A variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict that this variant eliminates 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 7/121814 control chromosomes at a frequency of 0.0000575, which does not exceed the estimated maximal expected allele frequency of a pathogenic CHEK2 variant (0.0003125). This variant has been reported in patients with breast cancer or colonrectal cancer (Susswein_2015, Rohlin_2016, Dominguez-Valentin_2017). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000545158 SCV000633168 likely pathogenic Familial cancer of breast 2018-11-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 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 (rs587782401, ExAC 0.03%). This variant has been reported in individuals affected with thyroid cancer, breast cancer, and colorectal cancer (PMID: 28608266, 26681312, 27696107). ClinVar contains an entry for this variant (Variation ID: 142352). 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: 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.
Mendelics RCV000545158 SCV000839501 likely pathogenic Familial cancer of breast 2018-07-02 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.