Table 3

Rare missense variant associations with BC by domain

Domain (AA Start-AA End) Case carriers Control carriers OR (95% CI) p Value Pdiff
ATM All rare missense4891751.18 (0.99 to 1.40)0.073
In any domain127371.44 (1.00 to 2.08)0.0590.24
Not in any domain3621381.10 (0.90 to 1.35)0.36
TAN (7-165)1710 0.71 (0.33 to 1.56)0.52
FAT (2097–2488)67181.56 (0.93 to 2.63)0.12
PI3K (2714–2961)4392.01 (0.98 to 4.12)0.074
FAT + PI3K domains 110 27 1.71 (1.12 to 2.61) 0.015
CHEK2 All rare missense162501.36 (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 domain47181.10 (0.64 to 1.89)0.85
FHA (113-191)47141.41 (0.78 to 2.56)0.32
Pkinase (220-486)68181.59 (0.94 to 2.67)0.10
PALB2 All rare missense174571.28 (0.95 to 1.73)0.12
In any domain132401.39 (0.97 to 1.98)0.0830.50
Not in any domain42171.04 (0.59 to 1.82)1.00
BRCA1 binding (1-319) 71 17 1.76 (1.03 to 2.98) 0.047
ChAM (395-466)1180.58 (0.23 to 1.43)0.34
RAD51/BRCA2 binding (853–1186)50151.40 (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 domain4511731.09 (0.92 to 1.31)0.33
  • Domain boundaries were determined from Pfam (ATM and CHEK2) or UniProt (PALB2).

  • BC, breast cancer.