• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CHEK2 (HGNC:16627) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
checkpoint kinase 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
RAD53
Alias symbols
CDS1, CHK2, HuCds1, PP1425, bA444G7
%HI
6.9(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
1.53(Read more about gnomAD LOEUF score)
Cytoband
22q12.1
Genomic Coordinates
GRCh37/hg19: chr22:29083731-29137822 NCBI Ensembl UCSC
GRCh38/hg38: chr22:28687743-28741834 NCBI Ensembl UCSC
MANE Select Transcript
NM_007194.4 ENST00000404276.6 (Read more about MANE Select)
Function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their act... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-27372
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
01/08/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 15122511
    The CHEK2 Breast Cancer Case-Control Consortium (2004) analyzed the frequency of the c.1100delC variant, which results in a frameshift and loss of function, in 10 case-control studies in five counties. 10860 individuals with breast cancer and 9065 unaffected controls were genotyped. CHEK2 c.1100delC was observed in 201 cases and 64 controls for an odds ratio of 2.34 (95% CI 1.72-3.20, p = .0000001), consistent with this variant increasing breast cancer risk in women unselected for family history.
  • PUBMED: 16897426
    Cybulski et al (2007) studied 4454 Polish women with breast cancer and 5496 population controls. Cases were genotyped for a 5395 bp deletion affecting exons 9 and 10 of the gene and had previously been genotyped for two other loss of function variants (c.1100delC and c.444+1G>A, referred to as IVS2+1G>A). The deletion was observed in .4% of controls and 1% of unselected breast cancer cases (OR 2.2, 95% CI:1.2-4.0; p = .01). When the three loss of function variants were considered as a group they were observed in 2.3% of cases and 1.1% of controls (OR 2.2, 95% CI: 1.6 -3.0; p<.0001).
  • PUBMED: 18381420
    Zhang et al (2008) analyzed the frequency of c.1100delC in 3882 breast cancer patient and 8609 controls from various ancestry groups. The CHEK2 variants were observed at significant rates in the group categorized as "white", consistent with the known founder effect in the European population. The study found that white women with nonfamilial breast cancer were more likely to have a variant than controls (OR 2.6, 95% CI 1.1-5.8, p.=. 05). White women with a family history of breast cancer were enriched for CHEK2 variants compared to controls (OR 5.2, 95% CI 2.6-10.5, p < .0001).
HI Evidence Comments:
Truncating mutations in CHEK2 are known to increased the risk of breast, as well as an increased risk for prostate cancer (Pritchard 2016 PMID 27433846).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No evidence for dosage pathogenicity due to triplosensitivity

Genomic View

Select assembly: (NC_000022.10) (NC_000022.11)