Germline variations predisposing to ALL include constitutional syndromes like Down syndrome[11], Noonan syndrome[12], familial cancer syndromes, Li-Fraumeni syndrome[13], constitutional mismatch repair deficiency syndrome[14, 15]), PAX5 mutations[16, 17], ETV6 variants [18, 19] as well as genes harboring germline non-silent variants presumed to confer a risk of sporadic ALL like NBN, FLT3, SH2B3, and CREBBP [2, 10]. The gene discussed is PAX5; the disease is acute lymphoblastic leukemia.