It is noteworthy that several of the genes associated with high risk of childhood cancer discovered in recent years were among the constrained genes, for example: ETV6, discovered in 201588–91, LOEUF = 0.318; FBXW7, discovered in 201992, LOEUF = 0.232; and, as discussed above, DIS3L2, discovered in 202282, LOEUF = 0.325 (Fig. 3C). Here, FBXW7 is linked to childhood malignant neoplasm.