ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1434del (p.Glu479fs) (rs786202601)

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
Ambry Genetics RCV000165489 SCV000216220 pathogenic Hereditary cancer-predisposing syndrome 2017-11-06 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 RCV000165489 SCV000911177 pathogenic Hereditary cancer-predisposing syndrome 2018-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000222773 SCV000279829 pathogenic not provided 2018-08-22 criteria provided, single submitter clinical testing This deletion of one nucleotide in CHEK2 is denoted c.1434delA at the cDNA level and p.Glu479LysfsX3 (E479KfsX3) at the protein level. The normal sequence, with the base that is deleted in brackets, is CAGA[delA]GAAG. The deletion causes a frameshift, which changes a Glutamic Acid to a Lysine at codon 479, and creates a premature stop codon at position 3 of the new reading frame. It is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. CHEK2 c.1434delA has been observed in at least two individuals referred for multi-gene hereditary cancer panel testing (Leedom 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000588604 SCV000698779 likely pathogenic Li-Fraumeni syndrome 2016-05-09 criteria provided, single submitter clinical testing Variant summary: The CHEK2 c.1434delA (p.Glu479Lysfs) variant results in a premature termination codon, predicted to cause a truncated or absent CHEK2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 113468 control chromosomes. In addition, one reputable clinical diagnostic laboratory has classified this variant as "pathogenic". The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000458226 SCV000550472 pathogenic Familial cancer of breast 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu479Lysfs*3) 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 been reported in with personal and/or family history of breast cancer (PMID: 27751358). ClinVar contains an entry for this variant (Variation ID: 185972). 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.