WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome

Table 2 WFS1 variants in the present study and its pathogenicity prediction analysis

Family	Genomic Position	HGVS				In Silico Prediction			MAF			ACMG/AMP 2018 Guideline
Family	Genomic Position	Coding DNA Change	Protein Change	Domain	Zygosity	CADD	REVEL	GERP	KRGDB (1722 individuals)	ExAC	gnomAD	Criteria	Classification
SH 486	Chr4: 6,303,067	c.1544_1545insA	p.Phe515LeufsTer28	TM6	Het	N/A	N/A	4.38	Absent	Absent	Absent	PVS1 PS2_Sup. PM2 PP4	Pathogenic
SH 550 SH 592	Chr4: 6,303,067	c.2051 C > T	p.Ala684Val	ER lumen	Het	28.8	0.891	5.49	Absent	Absent	0.000007	PS1 PS2_Sup. PM2 PP3 PP4	Pathogenic

Refseq transcript accession number NM_006005.3; Refseq protein accession number NP_005996.2.
HGVS: Human Genome Variation Society (https://www.hgvs.org/); Sequence Variant Nomenclature (http://varnomen.hgvs.org/); CADD: Combined Annotation Dependent Depletion (https://cadd.gs.washington.edu/); REVEL: Rare Exome Variant Ensemble Learner (https://sites.google.com/site/revelgenomics/); KRGDB: Korean Reference Genome Database (http://coda.nih.go.kr/coda/KRGDB/index.jsp); ExAC: Exome Aggregation Consortium databases; gnomAD: The Genome Aggregation Database (https://gnomad.broadinstitute.org/); ACMG/AMP 2018 guideline (http://wintervar.wglab.org/).
TM indicates transmembrane; Het, heterozygote; MAF, minor allele frequency; N/A, not available.

ISSN: 1755-8794