• Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit



CDS1; CHK2; HuCds1; LFS2; PP1425; RAD53; hCds1

Associated disorders

The CHEK2 gene is associated with an increased risk for autosomal dominant breast, colon, thyroid and prostate cancers (PMID: 15492928, 18759107, 21807500, 21876083, 25431674).

The gene CHEK2 (checkpoint kinase 2) encodes a cell cycle regulator and putative tumor suppressor. This protein is activated in response to DNA damage and inhibits CDC25C phosphatase, prevents entry into mitosis, and stabilizes the tumor suppressor protein p53. This leads to cell cycle arrest at the G1 phase. In addition, this protein interacts with phosphorylated BRCA1, allowing BRCA1 to restore survival after DNA damage.

OMIM: 604373

Clinical condition
The CHEK2 gene is associated with an increased risk for autosomal dominant adult-onset cancers, including breast, colon, thyroid, prostate, and possibly others (PMID: 15492928, 18759107, 21807500, 21876083, 25431674). The risks of these cancers, particularly breast, have been determined to be both variant- and family history-dependent (PMID: 20597917, 21876083).

Lifetime risks for female breast cancer related to frameshift variants, such as 1100delC, have been estimated to be 25-39% in heterozygotes (PMID: 18172190, 21876083). The risks for most missense variants are unclear, but risks for certain variants (such as p.Ile157Thr) are thought to be lower (PMID: 22799331, 23713947).

Individuals with two copies of the CHEK2 1100delC variant (i.e., those who are homozygous) have a higher breast cancer risk compared with those with a single copy (i.e., those who are heterozygous). The lifetime risk of breast cancer in individuals homozygous for this variant is estimated to be increased four to six fold (PMID: 22058428, 23652375). The estimates of other cancer risks among homozygotes or compound heterozygotes involving other variants is unclear.

Gene information
The CHEK2 gene encodes the CHEK2 enzyme, which helps to ensure accurate DNA repair. In this role, CHEK2 acts as a tumor suppressor by promoting stability of the genome and by preventing tumor formation. The CHEK2 gene is associated with the DNA damage repair response involving the Fanconi anemia-BRCA pathway (PMID: 19686080). A pathogenic variant that disrupts the function of CHEK2 decreases the ability of the cell to protect the integrity of the DNA (PMID: 25431674).

Hereditary predisposition to cancer due to pathogenic variants in the CHEK2 gene has autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the condition onto their offspring. This result allows for the identification of at-risk relatives who can pursue testing for this specific familial variant. Many cases are inherited from a parent, but some cases can occur spontaneously (i.e., an individual with a pathogenic variant has parents who do not have it).

Current screening guidelines from the National Comprehensive Cancer Network (NCCN) for those with a pathogenic CHEK2 variant are as follows:
Breast cancer:

  • Annual mammogram with consideration of tomosynthesis; also consider breast MRI with contrast beginning at age 40
  • Evidence of risk-reducing mastectomy is insufficient; manage based on family history
    Colon cancer:
  • Colonoscopy screening every 5 years beginning at age 40
    • If an individual has a first-degree relative with colorectal cancer, screening should begin 10 years prior to the relative’s age at diagnosis if before 40.
    • If an individual has a personal history of colorectal cancer, screening recommendations should be based on recommendations for post-colorectal cancer resection.

Additional publications underscore the appropriateness of breast MRIs and consideration of chemoprevention (tamoxifen) due to the greater than 20% lifetime risk of breast cancer associated with the 1100delC variant (PMID: 21876083, 20597917).

It has been suggested that men with a CHEK2 pathogenic variant and a first-degree relative with prostate cancer have an annual prostate-specific antigen (PSA) analysis (PMID: 20597917). However, the benefits of screening for prostate cancer among men with a pathogenic variant in CHEK2 are uncertain (PMID: 20597917).

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.

Knowing if a pathogenic CHEK2 variant is present is advantageous. At-risk relatives can be identified, enabling pursuit of a diagnostic evaluation. Information regarding hereditary cancer susceptibility genes is constantly evolving, and more clinically relevant data regarding CHEK2 is likely to become available in the near future. Awareness of this cancer predisposition encourages patients and their providers to inform at-risk family members, to diligently follow condition-specific screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.

Additional references
National Comprehensive Cancer Network. Breast and Ovarian Management Based on Genetic Test Results. Version 1.2018, accessed January 2018.

National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1.2018, accessed January 2018.

National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Colorectal. Version 3.2017, accessed January 2018.

Review date: January 2018

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CHEK2 NM_007194.3