Table 1.
Genes with ultra-rare variants enriched in non-syndromic clubfoot cases when compared with both gnomAD controls and in-house controls
| Gene | VAR_TYPE | Enrichment versus gnomAD | Enrichment versus in-house controls | ||||
| P_DOM | CASE (n=857) | CONTROL (n=56 885) | P_DOM | CASE (n=857) | CONTROL (n=1043) | ||
| ATP6V0D2 | Missense | 3.68E-06 | 7 | 37 | 4.12E-02 | 4 | 0 |
| COL15A1 | Missense | 1.05E-04 | 10 | 143 | 2.04E-02 | 10 | 3 |
| PHLDB1 | Missense | 3.15E-04 | 8 | 106 | 1.68E-03 | 8 | 0 |
| ZFYVE28 | Missense | 3.34E-04 | 8 | 107 | 2.75E-02 | 8 | 2 |
| PITX1 | All | 4.12E-04 | 6 | 59 | 8.34E-03 | 6 | 0 |
| MESD | All | 1.95E-03 | 4 | 32 | 4.12E-02 | 4 | 0 |
| RHOH | Missense | 1.95E-03 | 4 | 32 | 4.12E-02 | 4 | 0 |
| LMX1B | All | 3.02E-03 | 5 | 61 | 3.59E-02 | 6 | 1 |
| GLDC | Missense | 3.21E-03 | 9 | 191 | 2.55E-02 | 11 | 4 |
| PC | Missense | 3.43E-03 | 9 | 193 | 2.75E-02 | 8 | 2 |
| ATG2A | Missense | 4.04E-03 | 6 | 95 | 3.59E-02 | 6 | 1 |
| WDR7 | All | 4.34E-03 | 7 | 129 | 1.82E-02 | 7 | 1 |
| COL12A1 | All | 5.49E-03 | 13 | 372 | 2.14E-02 | 14 | 6 |
| G6PC1 | Missense | 6.85E-03 | 5 | 75 | 4.12E-02 | 4 | 0 |
| SUCLG2 | Missense | 6.85E-03 | 5 | 75 | 4.12E-02 | 4 | 0 |
| CATSPERG | Missense | 7.31E-03 | 3 | 24 | 1.86E-02 | 5 | 0 |
| COL9A3 | Missense | 7.87E-03 | 7 | 145 | 2.75E-02 | 8 | 2 |
| HPS6 | Missense | 7.98E-03 | 5 | 78 | 1.86E-02 | 5 | 0 |
| DNAH1 | Missense | 1.05E-02 | 13 | 405 | 3.42E-02 | 13 | 6 |
| ANKRD27 | Missense | 1.07E-02 | 6 | 118 | 3.59E-02 | 6 | 1 |
| BLTP3A | Missense | 1.22E-02 | 4 | 56 | 4.12E-02 | 4 | 0 |
| KDM5B | Missense | 1.24E-02 | 7 | 159 | 9.10E-03 | 8 | 1 |
| HOXD12 | Missense | 1.50E-02 | 3 | 32 | 1.86E-02 | 5 | 0 |
| VPS37D | All | 1.54E-02 | 2 | 11 | 4.12E-02 | 4 | 0 |
| MAPK7 | Missense | 1.68E-02 | 4 | 62 | 4.12E-02 | 4 | 0 |
| SLC26A2 | Missense | 1.97E-02 | 5 | 99 | 1.86E-02 | 5 | 0 |
| KRT28 | Missense | 2.04E-02 | 4 | 66 | 4.12E-02 | 4 | 0 |
| HSPG2 | Missense | 2.19E-02 | 16 | 595 | 4.64E-02 | 17 | 10 |
| XKR4 | All | 3.14E-02 | 4 | 76 | 4.12E-02 | 4 | 0 |
CASE, count in cases; CONTROL, count in controls; gnomAD TRAPD, TRAPD assay using gnomAD non-Finish European data; in-house TRAPD, TRAPD assay using in-house Caucasian controls; P_DOM, p value in dominant mode of TRAPD; TRAPD, Testing Rare vAriants using Public Data; VAR_TYPE, type of variants included in this burden analysis.