CanRisk considers the effects of heterozygous carriers of pathogenic truncating variants in the cancer susceptibility genes. Please see the explanation for this in the Discussion section of Lee et al., Genet. Med. 18, 1190–1198 (2016). In the rare situations of homozygous carriers, their risk of developing breast cancer will be the same as for heterozygous carriers (assuming a dominant model of inherence).When indicating an individual as a mutation "carrier", CanRisk assumes they are a heterozygous carrier by default.
However, the CanRisk tool should not be used in the case of a homozygous carrier in ATM, who would develop the condition Ataxia-Telangiectasia, and is known to be associated with a much higher risk of breast cancer. Similarly, Canrisk will underestimate the risk of breast cancer to homozygous carriers of pathogenic CHEK2 pathogenic truncating variants.
