Table 3

Rare missense variant associations with BC by domain

	Domain (AA Start-AA End)	Case carriers	Control carriers	OR (95% CI)	p Value	P_diff
*ATM*	All rare missense	489	175	1.18 (0.99 to 1.40)	0.073
	In any domain	127	37	1.44 (1.00 to 2.08)	0.059	0.24
	Not in any domain	362	138	1.10 (0.90 to 1.35)	0.36	0.24
	TAN (7-165)	17	10	0.71 (0.33 to 1.56)	0.52
	FAT (2097–2488)	67	18	1.56 (0.93 to 2.63)	0.12
	PI3K (2714–2961)	43	9	2.01 (0.98 to 4.12)	0.074
	FAT + PI3K domains	110	27	1.71 (1.12 to 2.61)	0.015
*CHEK2*	All rare missense	162	50	1.36 (0.99 to 1.87)	0.066
	In any domain	115	32	1.51 (1.02 to 2.24)	0.047	0.45
	Not in any domain	47	18	1.10 (0.64 to 1.89)	0.85	0.45
	FHA (113-191)	47	14	1.41 (0.78 to 2.56)	0.32
	Pkinase (220-486)	68	18	1.59 (0.94 to 2.67)	0.10
*PALB2*	All rare missense	174	57	1.28 (0.95 to 1.73)	0.12
	In any domain	132	40	1.39 (0.97 to 1.98)	0.083	0.50
	Not in any domain	42	17	1.04 (0.59 to 1.82)	1.00	0.50
	BRCA1 binding (1-319)	71	17	1.76 (1.03 to 2.98)	0.047
	ChAM (395-466)	11	8	0.58 (0.23 to 1.43)	0.34
	RAD51/BRCA2 binding (853–1186)	50	15	1.40 (0.79 to 2.49)	0.31
	Both binding domains	121	32	1.59 (1.08 to 2.35)	0.024
Combined	All rare missense	825	282	1.24 (1.08 to 1.43)	0.0025
	In any domain	374	109	1.45 (1.17 to 1.80)	7.3x10^-4	0.060
	Not in any domain	451	173	1.09 (0.92 to 1.31)	0.33	0.060

Domain boundaries were determined from Pfam (ATM and CHEK2) or UniProt (PALB2).
BC, breast cancer.