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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 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.