Table 2. Possibly damaging or well conserved variants in genes encoding proteins involved in DNA integrity maintaince.

Gene	Variant	Grantham	GERP1	PhastCons1	PolyPhen2	Function
CASC5	p.I26L	5	4.53	0.999	Probably damaging	Spindle-assembly checkpoint signaling and chromosome alignment
CUL9	p.S2328F	155	5.03	0.989	Possibly damaging	Regulates the subcellular localization of p53 and subsequent function
HLTF	p.S378T	58	3.15	0.208	Benign	Error-free postreplication repair of damaged DNA
MUTYH	p.I223V	29	5.43	1	Benign	Oxidative DNA damage repair
RBMX	p.Y357H	83	5.66	1	Probably damaging	Regulation of programmed cell death in breast cancer and homologous recombination
SMC6	p.R403W	101	2.65	0.998	Probably damaging	DNA damage repair via homologous recombination
TTK	p.R185W	101	4.04	0.004	Probably damaging	Chromosome alignment, centrosome duplication and critical mitotic checkpoint
XRCC2	p.R91W	101	4.48	0.742	Probably damaging	DNA damage repair via homologous recombination

Variants were selected if either of these criteria was met: Grantham score>100, GERP conservation score>3, PhastCons conservation score>0.7, or a “Probably damaging” Polyphen2 prediction.

¹Phastcons and GERP are both regional conservation algorithms ranging from 0 to 1 and −12.3 to 6.17 respectively (1 and 6.17 being most conserved).