Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

Table 4 Novel variations identified in ERCC6(CSB), ERCC8(CSA), ERCC2(XPD), ERCC3(XPB) ERCC5(XPG) and POLH genes

Gene	DNA variant	cDNA variant	Protein	Type (DNA)	Localization	Variant predicted effect	Functionnal domain	Frequency in EVSdb	Frequency in ExACdb	Prediction among SIFT and PolyPhen 2 and Mutation Taster	Patient #
ERCC6(CSB)	c.543G>T	r.423_543del (exon 3 deletion)	p.Lys181Asn	Substitution	exon 3	Missense + splicing	-	NF	NF	D, PD, DC	4
ERCC6(CSB)	c.4115delG	-	p.Gly1372Glufs*22	Deletion	exon 21	Frameshift	-	NF	NF	-	2
ERCC8(CSA)	c.356C>T	-	p.Ser119Leu	Substitution	exon 4	Missense	WD40	NF	NF	D, PD, DC	6
	c.730C>T	-	p.His244Tyr	Substitution	exon 9	Missense	WD40	NF	NF	D, PD, DC	8
	c.793A>C	-	p.Thr265Pro	Substitution	exon 9	Missense	WD40	NF	NF	D, PD, DC	9
	c.927delT	-	p.Phe309Leufs*19	Deletion	exon 10	Frameshift	-	NF	NF	-	5
	c.1041+1G>T	Not tested	p.?	Substitution	intron 10	Splicing	-	NF	NF	-	5
	c.1122+1delG	Not tested	p.?	Deletion	intron 11	Splicing	-	NF	NF	-	7
ERCC3(XPB)	c.325C>T	-	p.Arg109*	Substitution	exon 3	Nonsense	-	0.000462	0.000478	-	17
ERCC3(XPB)	c.2200-10C>G	r.2199_2200ins2200-9_2200-1 (partial insertion of intron 9)	p.Glu734_Thr1186delinsIleLeu*	Substitution	intron 9	Splicing	-	NF	NF	-	16
POLH	c.764+1G>A	r.723_764del42 (partial del exon 6)	p.Ser242_Ile255del14	Substitution	intron 6	Splicing	-	NF	8.241e-06	-	10, 11, 12, 13
		r.723_764del42 (partial del exon 6)	p.Val221Profs*2
		r.661_764del104 (del exon 6)	p.Val221Profs*2
POLH	c.1445C>A	-	p.Ser482*	Substitution	exon 11	Nonsense	-	NF	NF	-	10

D deleterious, DC disease causing, EVSdb Exome Variant Server database, ExACdb Exome Aggregation Consortium database, NF no frequency data available, PD probably damaging

ISSN: 1750-1172