Table 1. Rare missense, nonsense, and splicing variants reported in NSCL/P.
| Gene | Mutation | Polyphen 2 Prediction | Population | Cleft Type | NSCL/P cases | ESP6500 counts (N=13006) | 1kGP counts (N=2184) | Ref. |
|---|---|---|---|---|---|---|---|---|
| BMP4 | S91C | probably damaging | Spain | OO | 1 | 2 | 0 | (16) |
| BMP4 | T102A | benign | Philippines Mongolia | CLP | 2 | 0 | 2 | (16) |
| BMP4 | R162Q | probably damaging | Mongolia | CLP | 1 | 0 | 0 | (16) |
| BMP4 | G168A | benign | Philippines | CLP | 1 | 0 | 0 | (16) |
| BMP4 | R287H | benign | USA (PA) | OO | 1 | 18 | 2 | (16) |
| BMP4 | R198× | truncation | Mongolia | CLP | 1 | 0 | 0 | (16) |
| BMP4 | A346V | probably damaging | USA (WA) | MCL+BU | 1 | 0 | 0 | (16) |
| FGF8 | D73H | possibly damaging | USA (IA) | CLP, CP | 1 | 0 | 0 | (11) |
| FGFR1 | M369I | benign | Philippines | CP, CLP | 2 | 0 | 0 | (11) |
| FGFR1 | E467K | possibly damaging | Philippines | CLP | 2 | 0 | 0 | (11) |
| FGFR1 | R609× | truncation | USA (IA) | CLP | 1 | 0 | 0 | (11) |
| FGFR2 | R84S | probably damaging | USA (IA) | CLP | 1 | 0 | 0 | (11) |
| FGFR2 | D138N | possibly damaging | Philippines | CL/P | 5 | 0 | 0 | (11) |
| FOXE1 | A207V | probably damaging | Philippines | CLP | 1 | 0 | 0 | (17) |
| FOXE1 | D285V | possibly damaging | USA (IA) | CLP | 1 | 0 | 0 | (17) |
| GLI2 | R374H | probably damaging | USA (IA) | CLP | 1 | 1 | 0 | (17) |
| GLI2 | R754Q | probably damaging | Philippines | CLP | 1 | 4 | 0 | (17) |
| GLI2 | G1106D | benign | USA (IA) | CLP | 1 | 0 | 0 | (17) |
| GLI2 | S1541Y | probably damaging | Philippines | CLP | 1 | 0 | 2 | (17) |
| JAG2 | M559I | benign | USA (IA) | CLP | 1 | 4 | 0 | (17) |
| JAG2 | D657H | probably damaging | Philippines | CLP | 1 | 0 | 0 | (17) |
| MSX1 | M43L | benign | Malaysia | CLP | 1 | 0 | 0 | (18) |
| MSX1 | G97D | benign | Philippines | CP | 1 | 0 | 0 | (19) |
| MSX1 | V120G | benign | Denmark | CL | 1 | 0 | 0 | (19) |
| MSX1 | G122E | benign | Uruguay | CLP | 1 | 0 | 0 | (19) |
| MSX1 | R157S | possibly damaging | Japan | CLP | 1 | 0 | 19 | (19) |
| MSX1 | G273C | possibly damaging | Thailand | CLP | 1 | 0 | 0 | (20) |
| MSX1 | P284S | probably damaging | Thailand | CLP | 1 | 0 | 0 | (20) |
| MSX2 | S63C | possibly damaging | USA (IA) | CLP | 1 | 0 | 0 | (17) |
| NUDT6 | K172N | probably damaging | USA (IA) | CLP | 1 | 0 | 0 | (11) |
| PAX9 | S214G | benign | Japan | CL/P | 1 | 0 | 0 | (21) |
| PTCH1 | P295S | probably damaging | Philippines | CL/P | 1 | 0 | 0 | (22) |
| PVRL1 | V89M | probably damaging | N. America | CL/P | 2 | 0 | 0 | (23) |
| PVRL1 | S112T | benign | Philippines | CLP | 1 | 0 | 0 | (24) |
| PVRL1 | T131A | benign | Philippines | CLP | 1 | 0 | 1 | (24) |
| PVRL1 | R212H | probably damaging | Italy | CL/P | 1 | 11 | 6 | (25) |
| PVRL1 | IVS4+1 | splicing | Australia | CL/P | 1 | (23) | ||
| PVRL2 | E41K | possibly damaging | USA (IA) | CL/P | 1 | 2 | 0 | (26) |
| RYK | Y456C | probably damaging | Vietnam | CLP | 1 | 0 | 0 | (27) |
| SATB2 | T190A | possibly damaging | Philippines | CLP | 1 | 0 | 0 | (17) |
| SPRY2 | K68N | benign | USA (IA) | CLP | 1 | 1 | 0 | (17) |
| TGFB3 | K130R | benign | unspecified | SMCP | 1 | 0 | 0 | (28) |
| TP63 | S90L | possibly damaging | Thailand | CL | 1 | 0 | 1 | (10) |
| TP63 | R313G | probably damaging | Thailand | CL | 1 | 0 | 0 | (10) |
Bolded variants arose de novo
Abbreviations: CL- cleft lip; CLP- cleft lip and palate; CL/P- cleft lip with or without cleft palate; SMCP- submucous cleft palate; MCL- microform cleft lip; BU- bifid uvula