Candidate colorectal cancer predisposing gene variants in Chinese early-onset and familial cases

Table 6 In silico functional prediction of 16 missense variants

Sample ID	Gene name	Gene/pathway involved	cDNA change	Protein change	Domain	PhyloP score	Grantham score	Align GVGD	SIFT score	SIFT prediction	Polyphen2 score	Polyphen2 prediction
77-1A	LRP5	WNT	c.2156A>G	p.Tyr719Cys	LDLR class B repeat	4.751	194	C65	0.000	D	0.999	PrD
43-1A	LRP5	WNT	c.3536G>A	p.Arg1179His	LDLR class B repeat	3.712	29	C25	0.000	D	0.953	PrD
54-2A	LRP5	WNT	c.3919C>T	p.Arg1307Trp	LDLR class A repeat	3.172	101	C35	0.000	D	0.948	PrD
110-1A	RPS6KB2	PI3K/AKT	c.331A>G	p.Lys111Glu	Protein kinase, catalytic domain	4.639	56	C55	0.000	D	0.535	PoD
43-1A	RPS6KB2	PI3K/AKT	c.683C>A	p.Thr228Asn	Protein kinase, catalytic domain	5.062	65	C55	0.001	D	0.994	PrD
43-1A	RYR2	Somatic mutation gene	c.2701G>A	p.Gly901Ser	Ryanodine receptor	6.081	56	C55	0.010	D	1.000	PrD
103-1A	RYR2	Somatic mutation gene	c.6457A>G	p.Lys2153Glu	Intracellular calcium-release channel	5.067	56	C0	0.020	D	0.615	PoD
102-1A	RYR3	Somatic mutation gene	c.13507G>A	p.Val4503Met	Ryanodine Receptor TM 4-6	6.012	21	C15	0.000	D	1.000	PrD
71A	ETV4	Cancer gene	c.991G>A	p.Glu331Lys	PEA3-type ETS-domain transcription factor, N-terminal	6.424	56	C55	0.001	D	0.862	PoD
103-1A	PRDM1	Cancer gene	c.1499A>G	p.Gln500Arg	Zinc finger, C2H2	4.875	43	C0	0.050	D	0.570	PoD
164-1A	TSC2	Cancer gene, PI3K/AKT	c.5200G>A	p.Asp1734Asn	Rap/ran-GAP	5.538	23	C0	0.000	D	0.998	PrD
71A	MTOR	PI3K/AKT	c.5857G>T	p.Val1953Leu	PIK-related kinase	5.634	32	C0	0.001	D	0.827	PoD
154-1A	DAAM1	WNT	c.667G>A	p.Val223Met	Diaphanous GTPase-binding	6.347	21	C0	0.000	D	0.998	PrD
71A	FZD10	WNT	c.1341C>G	p.Phe447Leu	Frizzled protein	4.229	22	C15	0.000	D	0.984	PrD
164-1A	TCF7	WNT	c.572G>T	p.Arg191Met	High mobility group, HMG1/HMG2	4.202	91	C65	0.000	D	0.999	PrD
71A	MAST2	Transposon studies	c.3482A>G	p.Asn1161Ser	PDZ/DHR/GLGF	4.854	46	C0	0.000	D	0.999	PrD

D: Damaging; PoD: Possibly damaging; PrD: Probably damaging.