Table 2.

Pathogenic variants of USH2A and its pathogenic potential according to in-silico analysis and ACMG-AMP guideline

Gene	Family ID	Variant	State	Prediction algorithm			Conservation score		MAF		Reported/study	ACMG/AMP guideline
				Mutation taster	PP-2	SIFT	PhyloP	GERP++	GMAF	KRGDB
USH2A (NM_206933)	SB 237-461	c.8167C>T: p.R2723X	Het	DC	NA	NA	0.953	–0.488	0.00001 (1/121224, ExAC)	Absent	Reported/Jaijo et al. [23]	“Pathogenic” (PVS1, PM2, PM4, PP4)
									0.00002 (1/5008, 1000G)
									0.00001 (1/125568 TOPMED)
									0.000004 (1/245742, GnomAD)
		c.1823G>A: p.C608Y	Het	DC	PD	D	4.66	4.61	Absent	Absent	Novel/this study	“Uncertain significance” (PM2, PP3, PP4)
	SB 354-692	c.14835del: p.S4945fs*4	Het	DC	NA	NA	–0.825	–5.19	Absent	Absent	Novel/this study	“Pathogenic” (PVS1, PM2, PM4, PP4)
		c.13112_13115del: p.G4371fs*19	Het	DC	NA	NA	4.88	5.12	0.00002 (3/121124, ExAC)	0.00029 (1/3444)	Reported/Sengillo et al. [24]	“Pathogenic” (PVS1, PM2, PM4, PP4)
									0.00003 (4/125568, TOPMED)
									0.00001 (3/245602, GnomAD)

ACMG AMP, American College of Medical Genetics and Genomics/Association for Molecular Pathology; MAF, minor allele frequency; GMAF, global minor allele frequency; KRGDB, Korean Reference Genome Database; Het, heterozygous; DC, disease causing; NA, not available; ExAC, Exome Aggregation Consortium; PD, probable damaging; D, damaging.