Table 2.
Pathogenic Variants Detected in FZD4
| No | Number | Exon | Nucleotide Changes | Protein Change | Type | 1000G | ExAC | SIFT | Poly-Phen2 | CADD | REVEL | Mutation Taster | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 1 | 1 | c.49_50insCCCGGGGGCG | p.Val17Alafs*116 | Insertion | 0 | 0 | – | – | – | – | – | Novel |
| 2 | 2 | 1 | c.107G>A | p.Gly36Asp | Missense | 0 | 0 | D | B | 0.51388 | 0.374 | A | 23 |
| 3 | 2 | 1 | c.118G>T | p.Glu40* | Nonsense | 0 | 0 | T | P | 0.09039 | 0.511 | – | 11 |
| 4 | 1 | 1 | c.133T>C | p.Cys45Arg | Missense | 0 | 0 | D | D | 0.80669 | 0.967 | D | 17 |
| 5 | 1 | 1 | c.134G>A | p.Cys45Tyr | Missense | 0 | 0 | D | D | 0.88401 | 0.944 | D | 24 |
| 6 | 1 | 1 | c.133T>A | p.Cys45Ser | Missense | 0 | 0 | D | P | 0.72502 | 0.95 | D | 17 |
| 7 | 1 | 1 | c.141dup | p.Ile48Hisfs*82 | Insertion | 0 | 0 | – | – | – | – | – | Novel |
| 8 | 1 | 1 | c.158G>C | p.Cys53Ser | Missense | 0 | 0 | D | D | 0.82476 | 0.986 | D | 17 |
| 9 | 1 | 1 | c.169G>C | p.Gly57Arg | Missense | 0 | 0 | D | D | 0.88966 | 0.93319 | D | Novel |
| 10 | 1 | 1 | c.182C>T | p.Thr61Ile | Missense | 0 | 0 | D | D | 0.87976 | 0.93 | D | 18 |
| 11 | 3 | 1 | c.205C>T | p.His69Tyr | Missense | 0.0002 | 0.000562 | D | B | 0.76753 | 0.663 | A | 22 |
| 12 | 1 | 1 | c.223G>A | p.Ala75Thr | Missense | 0 | 0.000009 | D | D | 0.9522 | 0.875 | D | 17 |
| 13 | 1 | 1 | c.260del | p.Gln87Argfs*46 | Deletion | 0 | 0 | – | – | – | – | – | Novel |
| 14 | 1 | 1 | c.264C>A | p.Tyr88* | Nonsense | 0 | 0 | – | – | – | – | – | 21 |
| 15 | 1 | 1 | c.268T>C | p.Cys90Arg | Missense | 0 | 0 | D | D | 0.85883 | 0.965 | D | 17 |
| 16 | 1 | 1 | c.284A>T | p.Gln95Leu | Missense | 0 | 0 | D | B | 0.50873 | 0.487 | D | Novel |
| 17 | 1 | 1 | c.285G>A | p.Gln95Gln | Synonymous | 0 | 0 | – | – | – | – | – | Novel |
| 18 | 12 | 2 | c.313A>G | p.Met105Val | Missense | 0 | 0.000017 | T | P | 0.09039 | 0.511 | A | 25 |
| 19 | 1 | 2 | c.316_317dup | p.Thr107Alafs*27 | Frameshift | 0 | 0 | – | – | – | – | – | Novel |
| 20 | 1 | 2 | c.341T>C | p.Ile114Thr | Missense | 0 | 0 | D | P | 0.71563 | 0.851 | D | 20 |
| 21 | 1 | 2 | c.351C>G | p.Cys117Trp | Missense | 0 | 0 | D | D | 0.39612 | 0.563 | D | Novel |
| 22 | 1 | 2 | c.380del | p.Arg127Profs*6 | Deletion | 0 | 0 | – | – | – | – | – | 29 |
| 23 | 1 | 2 | c.451C>T | p.Gln151* | Nonsense | 0 | 0 | – | – | – | – | – | Novel |
| 24 | 1 | 2 | c.456C>A | p.Asn152Lys | Missense | 0 | 0 | T | D | 0.23802 | 0.533 | D | Novel |
| 25 | 1 | 2 | c.485del | p.Pro162Glnfs*33 | Deletion | 0 | 0 | – | – | – | – | – | Novel |
| 26 | 1 | 2 | c.541T>C | p.Cys181Arg | Missense | 0 | 0 | T | B | 0.4704 | 0.77591 | A | 28 |
| 27 | 1 | 2 | c.551_552del | p.Val184Glyfs*5 | Deletion | 0 | 0 | – | – | – | – | – | Novel |
| 28 | 1 | 2 | c.579G>A | p.Trp193* | Nonsense | 0 | 0 | – | – | – | – | – | Novel |
| 29 | 1 | 2 | c.631T>C | p.Tyr211His | Missense | 0 | 0 | D | B | 0.43228 | 0.35 | D | 19 |
| 30 | 1 | 2 | c.716T>C | p.Leu239Pro | Missense | 0 | 0 | D | D | 0.70572 | 0.727 | D | 26 |
| 31 | 1 | 2 | c.757C>T | p.Arg253Cys | Missense | 0 | 0 | D | D | 0.87568 | 0.595 | D | 20 |
| 32 | 1 | 2 | c.930C>G | p.Tyr310* | Nonsense | 0 | 0 | – | – | – | – | – | Novel |
| 33 | 2 | 2 | c.957G>A | p.Trp319* | Nonsense | 0 | 0 | – | – | – | – | – | 22 |
| 34 | 1 | 2 | c.974T>G | p.Leu325Arg | Missense | 0 | 0 | D | D | 0.70193 | 0.76 | D | Novel |
| 35 | 1 | 2 | c.975_978del | p.Thr326Glyfs*31 | Deletion | 0 | 0 | – | – | – | – | – | 17 |
| 36 | 1 | 2 | c.1000-1001insCTCA | p.Lys334Thrfs*6 | Insertion | 0 | 0 | – | – | – | – | – | Novel |
| 37 | 1 | 2 | c.1034_1054del | p.Ser345_Ala351del | Deletion | 0 | 0 | – | – | – | – | – | 17 |
| 38 | 1 | 2 | c.1155del | p.Asp385Glufs*46 | Frameshift | 0 | 0 | – | – | – | – | – | Novel |
| 39 | 1 | 2 | c.1181C>T | p.Pro394Leu | Missense | 0 | 0 | D | D | 0.79179 | 0.896 | D | Novel |
| 40 | 10 | 2 | c.1282_1285del | p.Asp428Serfs*2 | Deletion | 0 | 0 | – | – | – | – | – | 18 |
| 41 | 1 | 2 | c.1293_1296del | p.Glu431Aspfs*2 | Deletion | 0 | 0 | – | – | – | – | – | Novel |
| 42 | 1 | 2 | c.1310T>C | p.Ile437Thr | Missense | 0 | 0 | D | D | 0.64757 | 0.943 | D | 20 |
| 43 | 1 | 2 | c.1328_1332del | p.Leu443Hisfs*14 | Deletion | 0 | 0 | – | – | – | – | – | Novel |
| 44 | 1 | 2 | c.1475del | p.Gly492Alafs*21 | Deletion | 0 | 0 | – | – | – | – | – | 17 |
| 45 | 1 | 2 | c.1478-79insAT | p.Met493Ilefs*21 | Deletion | 0 | 0 | – | – | – | – | – | Novel |
| 46 | 1 | 2 | c.1492_1502del | p.Ala498Serfs*33 | Deletion | 0 | 0 | – | – | – | – | – | Novel |
| 47 | 1 | 2 | c.1498del | p.Thr500Leufs*13 | Deletion | 0 | 0 | – | – | – | – | – | 23 |
| 48 | 6 | 2 | c.1589G>A | p.Gly530Glu | Missense | 0 | 0.000173 | D | P | 0.46364 | 0.787 | D | 20 |
| 49 | 1 | Intron 1 | c.286-3G>C | – | Splicing | 0 | 0 | – | – | – | – | Splice site change | Novel |
| 50 | 4 | 1-2 | CNV (exon1-2 deletion) | – | CNV | 0 | 0 | – | – | – | – | – | 27 |
| 51 | 1 | Intron 1 | c.286-2A>G | – | Splicing | 0 | 0 | – | – | – | – | Splice site change | Novel |
T, tolerant; B, benign; D, damaging or disease causing; P, possibly damaging, A, disease causing automatic; N, polymorphism; P, polymorphism.
CNV, copy number variants.