We recently reported that a sequence variant in the cell-cycle-checkpoint kinase 
CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele 
in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 
variants confer susceptibility to breast cancer, we screened the full CHEK2 
coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with 
three or more cases of breast cancer. We identified one novel germline variant, 
R117G, in two separate families. To evaluate the possible association of R117G 
and two germline variants reported elsewhere, R145W and I157T with breast 
cancer, we screened 737 BRCA1/2-negative familial breast cancer cases from 605 
families, 459 BRCA1/2-positive cases from 335 families, and 723 controls from 
the United Kingdom, the Netherlands, and North America. All three variants were 
rare in all groups, and none occurred at significantly elevated frequency in 
familial breast cancer cases compared with controls. These results indicate that 
1100delC may be the only CHEK2 allele that makes an appreciable contribution to 
breast cancer susceptibility.