Though functional validation studies are required to substantiate the role of these variants in hyperdiploid pre-B childhood ALL, our data suggest that concomitant inheritance of rare variants in FA genes FANCA, FANCP/SLX4, in combination with rare mutations in the endonuclease GEN1 and the meiotic recombination gene PRDM9, could lead to increased DNA damage and genomic instability, and thus contribute to hyperdiploid leukemia predisposition. Here, GEN1 is linked to leukemia.