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A 50-year-old woman is diagnosed with breast cancer. Her mother had breast cancer at 55, and her maternal uncle had colorectal cancer. Genetic testing reveals a CHEK2 c.1100delC pathogenic variant.

AD; CHEK2 (checkpoint kinase 2)

  • DNA damage checkpoint response
  • c.1100delC founder variant common in Northern European populations
  • Moderate-penetrance breast cancer gene
  • Often hormone receptor-positive breast cancers
  • Less severe phenotype than BRCA1/2
  • c.1100delC variant creates truncated protein
  • Confirmed by germline testing identifying a pathogenic CHEK2 variant, usually on a multigene cancer panel rather than single-gene testing
  • The c.1100delC truncating variant is the most common pathogenic allele; missense variants (e.g., p.Ile157Thr) confer lower risk
  • Distinguish moderate-penetrance CHEK2 from high-penetrance BRCA1/BRCA2, since management and cascade-testing counseling differ
  • Enhanced breast surveillance (earlier mammograms, consider MRI)
  • Colonoscopy starting age 40 or 10 years before youngest family diagnosis
  • Risk-reducing mastectomy generally NOT recommended (lower penetrance)
  • No RRSO recommendation

"CHEK2 = CHEst Kancer from Chr 22": CHEK2 is on chromosome 22 and is associated with breast (chest) cancer.

"CHEK-ERS" checkered pattern: CHEK2 is associated with ER-positive breast cancer. Get a CHEK-up for breast cancer.

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