Table 3.

List of the most recurrently affected genes by rare and predictively disruptive germline variants. Genes in the top 0.5% of the FLAGS list are indicated, as well as predicted loss-of-function (pLOF) observed vs. expected ratio (o/e ratio) along with its 90% confidence interval.

Gene	No. Cases	FLAGS Top 0.5%	pLOF o/e Ratio
FAT3	32	Yes	0.18 [0.13–0.25]
SYNE1	31	Yes	0.37 [0.33–0.42]
FAT1	29	Yes	0.34 [0.27–0.43]
ATM	25	No	0.6 [0.51–0.71]
BIRC6	24	No	0.07 [0.04–0.1]
CLTCL1	24	No	0.8 [0.66–0.98]
ZFHX3	23	Yes	0.08 [0.05–0.14]
TSC2	22	No	0.02 [0.01–0.07]
CSMD3	21	No	0.23 [0.18–0.3]
MYH9	20	No	0.04 [0.02–0.09]
TPR	19	No	0.06 [0.04–0.11]
LRP1B	19	Yes	0.26 [0.21–0.32]
ANK1	19	No	0.1 [0.06–0.17]
EPPK1	19	Yes	0.96 [0.78–1.2]
KMT2D	19	Yes	0.07 [0.04–0.1]
PTPN13	18	No	0.52 [0.42–0.64]
MYH11	18	No	0.22 [0.16–0.3]
POLQ	17	No	1.05 [0.9–1.22]
KMT2C	17	Yes	0.08 [0.06–0.12]
MUC4	16	No	0.84 [0.7–0.99]
APC	16	No	0.1 [0.06–0.16]
ROS1	16	No	0.95 [0.82–1.12]
POLE	16	No	0.52 [0.42–0.64]
NBEA	16	No	0.04 [0.02–0.07]
SPEN	15	No	0.03 [0.01–0.07]
SETDB1	15	No	0.11 [0.06–0.2]
LPP	15	No	0.32 [0.19–0.56]
FAT4	15	Yes	0.12 [0.08–0.18]