For instance TRRAP, PREX2, SOX17, ZFHX4, MYC, KIT, KDR and other genes are suggestive examples of genes from this group showing negative selection signals in apparently noncognate cancer types (Fig. 2d, lower panel) with the effect sizes (log2 relative mutation risk depletion compared to baseline) ranging from −5.49 to −2.74 for top-10 hits without positively selected hotspots, with individually significant FDR ≤ 25% for some of them (KDR in GIST and TGCT, ZFHX4 in SKCM, SOX17 in UCEC-POLE and SKCM). Here, ZFHX4 is linked to cancer.