Table 2.

Details of seven predicted missense variants which were validated by Sanger sequencing

Gene (NCBI Ref Seq)	Mutation	Tumour ID	Functions, pathways	SIFT / MT / PolyPhen-2	CADDa	z-Scoreb	%ExAC_RVISc	TCGA / COSMIC	gnomAD	final assessment patho-genicity
ABI3BP (NM_015429.3)	c.2036A > T; p.K679 M	T71	prevention of tumorigenesis, proliferation of replicative senescence	D / DC / PD	24.6	−0.39	89.49	no report	no report	likely pathogenic
CALD1 (NM_033140.3)	c.332G > A; p.R111Q	T69	potent repressor of cancer cell invasion; Schwann cell migration	D / P / N/A	26.2	0.24	62.76	no report	2.481e-5	VUS
CATSPERB (NM_024764.2)	c.2309C > A; p.P770H	T71	spermatogenesis, cell differentiation, multicellular organism development	D / DC / PD	24.6	0.93	4.00	no report	no report	likely pathogenic
CCBP2 (NM_001296.4)	c.184A > T; p.S62C	T72	G-protein coupled receptor signaling pathway	T / P / B	0.006	−0.32	53.24	no report	no report	likely benign
COL8A1 NM_020351.3)	c.373G > A; p.E125K	T71	migration and proliferation of vascular smooth muscle cells	T / DC / B	13.1	0.59	10,36	no report	no report	VUS
DNAI1 (NM_012144.2)	c.1156G > A; p.V386I	T71	epithelial cilium movement, cell projection organization	T / P / B	11.3	−0.22	68.31	no report / 1 reportd	2.832e-5	likely benign
VGLL2 (NM_182645.2)	c.132C > A; p.S44R	T70	muscle differentiation and development of skeletal muscles	T / DC / PD	22.4	1.47	67.74	no report	no report	VUS

B benign, D damaging, DC disease causing, MT MutationTaster, N/A not applicable, P polymorphism, PD probably damaging, T tolerated, VUS variant of uncertain significance; ^acutoff on deleteriousness >15; ^bpositive Z scores indicate increased constraint (intolerance to variation), negative score implied that the gene shows more variants than expected; ^c values represent percentiles of %ExAC_RVIS scores. High values refer to tolerant genes while low values refer to intolerant genes; ^d in liver hepatocellular carcinoma