Molecular Vision: Jiang, Mol Vis 2021; 27:50-60. Table 1

Table 1. Rare variants in FZD5 predicted to be potentially damaging.

Variants	Position at	NM_003468	NM_003468.3	REVEL	CADD	SIFT	Polyphen-2	PROVEAN	GnomAD	ACMG classification [21]	Family
Variants	chr2 (hg19)	Change	Effect	score	score	score	score	pred	Allele		ID
1	2.1E+08	c.1510A>T	p.Met504Leu	0.828	26.3	D (0.011)	PB (0.854)	D	1/143348	PP=PS4,PP2, PP3	1267, 9472
2	2.1E+08	c.1428delG	p.Ser477 Alafs*130	/	/	/	/	/	0	p=PVS1,PS4, PM2,PP1,PP4	9574
3	2.1E+08	c.1403_1406'dupACCT	p.Tyr470 Profs*130	/	/	/	/	/	0	p=PVS1,PS4, PM2,PP1,PP4	5485
4	2.1E+08	c.1232A>G	p.Tyr411Cys	0.936	29.4	D (0.001)	PD (1.000)	D	1/143012	PP=PS4,PP2,PP3	18739
5	2.1E+08	c.1162G>A	p.Gly388Ser	0.972	29.9	D (0.000)	PD (1.000)	D	0	PP=PS4,PM2, PP1-PP4	12467
6	2.1E+08	c.794G>T	p.Arg265Leu	0.566	27.6	T (0.055)	PB (0.617)	D	0	PP=PS4,PM2, PP2	13706
7	2.1E+08	c.388C>A	p.Arg130Ser	0.594	24.3	T (0.275)	PB (0.835)	D	0	PP=PS4,PM2, PP4	17413
8	2.1E+08	c.350_356delCGCCGCT	p.Ser117*	/	/	/	/	/	0	p=PVS1,PS4, PM2	940

Note: In gnomAD, 5% of variants had REVEL or CADD scores greater than 0.856 or 29.1, while 75% had scores less than 0.613 or 25.1, respectively. None of the nine variants was present in HGMD, p = pathogenic, PP = possibly pathogenic, D = damaging, PD = probably damaging, PB = possibly damaging, T = tolerated. According to the ACMG criteria: PVS1 = predicted null variant in a gene where LOF is a known mechanism of disease; PS4 = prevalence in affected statistically increased over controls; PM2 = absent in population database, PP1 = cosegregation with diseases in multiple affected patients, PP2 = missense in gene with low rate of benign missense variants and pathogenic missense common; PP3 = multiple lines of computational evidence support a deleterious effect on the gene/gene product; PP4 = patient’s phenotype or FH highly specific for gene.