This is exemplified by the wide spectrum of ALL risk alleles identified in ETV6 in our current study: close to 1% of unselected sporadic ALL cases carry likely damaging and potentially highly penetrant germline risk variants in a single gene ETV6. Our findings challenge the current paradigm that ALL is primarily driven by somatic genetic alterations and imply that the inherited genetic predisposition to this cancer may be much greater than previously believed. Here, ETV6 is linked to acute lymphoblastic leukemia.