POLR2A and cancer: The same pattern of low allelic ratio was also observed for the coding variants (S3A Table); hence, although some candidate pathogenic mutations were identified in the coding region of genes that have been associated previously with cancer, such as MAP3K1 [32], FAT1 [33], POLR2A [34], LRP5 [35] and PRPF8 [36], the low allelic ratio (median = 32.6%; range: 16–55%) at which the variants were observed in SpTs (S3A Table) is not mechanistically consistent with a pathogenic role for a driver mutation.