Molecular investigation, using chromosomal microarray and whole exome sequencing, of six patients affected by Williams Beuren syndrome and Autism Spectrum Disorder

Table 2 Annotation of 6 exonic variants of unknown significance, found by WES in the recruited patients

WBS patients	1	2	3	3	3	3
Exome analysis	Trio	Trio	Solo	Solo	Solo	Solo
Variant	Chr16:2647248 A > G	Chr22:38642099A > G	Chr3:196612953 T > A	Chr6:15496807 G > C	Chr6:30919581 C > T	Chr13:35716473 A > G
Gene	PDPK1	TMEM184B	SENP5	JARID2	DPCR1	NBEA
Transcript	NM_002613.4	NM_001195072.1	NM_152699.4	NM_004973.3	NM_080870.3	NM_015678.4
Nucleotide variant	c.1526A > G	c.2 T > C	c.901 T > A	c.1351G > C	c.3340C > T	c.2404A > G
Protein variant	p.Lys509Arg	p.Met1?	p.Cys301Ser	p.Glu451Gln	p.Pro1114Ser	p.Thr802Ala
Variant effect	Missense	Start lost	Missense	Missense	Missense	Missense
Genotype	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous
ExAC occurrence	0	0	0	0	1	0
Inheritance	de novo	de novo	ND	ND	ND	ND
Cerebral expression (GTEx)	+	+	+	+	–	+
SIFT, Polyphen2, Mutation Taster	P, P, P	C, B, P	B, B, P	C, C, P	NA, I, B	B, I, P
Arguments	Reported in neurodevelopmental syndrome [12]	Gene function [13]	Animal study [14]	Reported in association with autism [15, 16]	Reported in association with neuropsychiatric disorders [17]	Autism candidate gene [18, 19]

WES whole exome sequencing, WBS Williams Beuren Syndrome, NA not available, ND not done, P pathogenic, C contradictory, B benign, I intermediary

ISSN: 1750-1172