Table 1.
Genes that reach de novo (DN) significance.
| smMIP screening | Published exomes | Total | FDR-corrected DN p-valueα | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||
| Gene | DN LGD | DN MIS30 | Probands screened | DN LGD | DN MIS30 | Probands screened | DN LGD | DN MIS30 | LGD | MIS30 | Study |
| SCN2A | 10 | 1 | 13407 | 11 | 6 | 5237 | 21 | 7 | 8.45E-45 | 1.27E-12 | GOLD |
| CHD8 | 5 | 0 | 13407 | 12 | 2 | 6158 | 17 | 2 | 4.26E-33 | 9.48E-03 | GOLD |
| POGZ | 4 | 1 | 13407 | 5 | 1 | 5237 | 9 | 2 | 2.06E-22 | 4.95E-04 | GOLD |
| MED13L | 2 | 0 | 13407 | 6 | 2 | 6158 | 8 | 2 | 1.98E-12 | 1.40E-02 | GOLD |
| STXBP1 | 1 | 0 | 13407 | 5 | 2 | 6158 | 6 | 2 | 2.03E-11 | 7.73E-03 | GOLD |
| GRIN2B | 2 | 1 | 13407 | 4 | 1 | 6158 | 6 | 2 | 6.39E-10 | 9.56E-03 | GOLD |
| KMT5B | 2 | 1 | 12192 | 3 | 1 | 5237 | 5 | 2 | 1.21E-09 | 1.93E-03 | ASD4 |
| TRIP12 | 2 | 0 | 13407 | 4 | 2 | 6158 | 6 | 2 | 1.84E-09 | 1.80E-02 | GOLD |
| CHD2 | 0 | 3 | 13407 | 7 | 1 | 6158 | 7 | 4 | 1.98E-08 | 7.66E-04 | GOLD |
| ASH1L | 2 | 2 | 13407 | 3 | 0 | 5237 | 5 | 2 | 2.26E-07 | 1.80E-02 | GOLD |
| SLC6A1 | 2 | 0 | 13407 | 1 | 2 | 6158 | 3 | 2 | 1.75E-04 | 2.49E-02 | GOLD |
| CASK | 0 | 0 | 12192 | 2 | 2 | 5237 | 2 | 2 | 1.09E-03 | 2.98E-03 | ASD4 |
| RELN | 2 | 1 | 13407 | 1 | 2 | 5237 | 3 | 3 | 1.27E-02 | 1.40E-02 | GOLD |
| ARID1B | 6 | 0 | 13407 | 16 | 0 | 5237 | 22 | 0 | 9.84E-42 | 1.00 | GOLD |
| ADNP | 7 | 0 | 13407 | 9 | 0 | 6158 | 16 | 0 | 9.57E-34 | 1.00 | GOLD |
| SYNGAP1 | 1 | 0 | 13407 | 16 | 1 | 6158 | 17 | 1 | 2.52E-27 | 0.19 | GOLD |
| DYRK1A | 2 | 0 | 13407 | 8 | 0 | 6158 | 10 | 0 | 1.32E-19 | 1.00 | GOLD |
| CTNNB1 | 0 | 0 | 13407 | 7 | 0 | 6158 | 7 | 0 | 4.34E-13 | 1.00 | GOLD |
| ANKRD11 | 0 | 0 | 12192 | 10 | 0 | 5237 | 10 | 0 | 4.34E-13 | 1.00 | ASD5 |
| NAA15 | 4 | 0 | 12192 | 2 | 0 | 5237 | 6 | 0 | 1.52E-12 | 1.00 | ASD4 |
| FOXP1 | 2 | 0 | 13407 | 4 | 0 | 5237 | 6 | 0 | 5.90E-12 | 1.00 | GOLD |
| TCF4 | 4 | 0 | 12192 | 3 | 1 | 5237 | 7 | 1 | 6.26E-12 | 0.22 | ASD4 |
| MECP2 | 2 | 0 | 11731 | 3 | 1 | 5237 | 5 | 1 | 4.12E-11 | 1.94E-02 | ASD6 |
| WAC | 1 | 0 | 13407 | 4 | 0 | 6158 | 5 | 0 | 9.63E-10 | 1.00 | GOLD |
| DSCAM | 2 | 0 | 13407 | 4 | 0 | 6158 | 6 | 0 | 7.89E-08 | 1.00 | GOLD |
| KMT2A | 0 | 0 | 11731 | 6 | 0 | 5237 | 6 | 0 | 8.57E-08 | 1.00 | ASD6 |
| CUL3 | 2 | 0 | 13407 | 2 | 0 | 5237 | 4 | 0 | 1.63E-07 | 1.00 | GOLD |
| TCF7L2 | 0 | 0 | 13407 | 3 | 0 | 6158 | 3 | 0 | 6.97E-05 | 1.00 | GOLD |
| ILF2 | 0 | 0 | 11731 | 2 | 0 | 5237 | 2 | 0 | 7.01E-05 | 1.00 | ASD6 |
| DDX3X | 0 | 0 | 13407 | 3 | 1 | 5237 | 3 | 1 | 9.95E-05 | 0.15 | GOLD |
| RIMS1 | 1 | 0 | 12192 | 2 | 0 | 5237 | 3 | 0 | 9.95E-05 | 1.00 | ASD4 |
| KATNAL2 | 1 | 1 | 13407 | 2 | 0 | 5237 | 3 | 1 | 1.00E-04 | 0.19 | GOLD |
| NCKAP1 | 1 | 0 | 12192 | 2 | 0 | 6158 | 3 | 0 | 1.43E-04 | 1.00 | ASD5 |
| SETBP1 | 0 | 0 | 13407 | 3 | 0 | 5237 | 3 | 0 | 1.50E-04 | 1.00 | GOLD |
| WDR45 | 0 | 0 | 11731 | 2 | 0 | 5237 | 2 | 0 | 1.75E-04 | 1.00 | ASD6 |
| SPAST | 0 | 0 | 12192 | 2 | 0 | 5237 | 2 | 0 | 1.80E-04 | 1.00 | ASD4 |
| PTEN | 0 | 0 | 13407 | 2 | 0 | 6158 | 2 | 0 | 2.46E-04 | 1.00 | GOLD |
| MYT1L | 1 | 0 | 11731 | 2 | 0 | 6158 | 3 | 0 | 3.29E-04 | 1.00 | ASD6 |
| TNRC6B | 1 | 0 | 13407 | 2 | 0 | 5237 | 3 | 0 | 3.49E-04 | 1.00 | GOLD |
| SETD5 | 0 | 1 | 13407 | 3 | 0 | 6158 | 3 | 1 | 3.61E-04 | 0.14 | GOLD |
| NRXN1 | 0 | 0 | 11731 | 3 | 0 | 6158 | 3 | 0 | 3.69E-04 | 1.00 | ASD6 |
| TBR1 | 0 | 0 | 13407 | 2 | 0 | 6158 | 2 | 0 | 5.21E-04 | 1.00 | GOLD |
| PAX5 | 0 | 0 | 13407 | 2 | 0 | 6158 | 2 | 0 | 1.13E-03 | 1.00 | GOLD |
| PPM1D | 0 | 0 | 13407 | 2 | 0 | 6158 | 2 | 0 | 2.73E-03 | 1.00 | GOLD |
| ANK2 | 0 | 1 | 12192 | 4 | 1 | 5237 | 4 | 2 | 2.93E-03 | 0.19 | ASD5 |
| HIVEP3 | 2 | 0 | 13407 | 1 | 0 | 5237 | 3 | 0 | 3.07E-03 | 1.00 | GOLD |
| CDC42BPB | 0 | 0 | 12192 | 2 | 0 | 5237 | 2 | 0 | 3.51E-03 | 1.00 | ASD4 |
| CACNA2D3 | 0 | 0 | 11731 | 2 | 0 | 5237 | 2 | 0 | 3.54E-03 | 1.00 | ASD6 |
| GIGYF2 | 1 | 0 | 13407 | 1 | 0 | 5237 | 2 | 0 | 3.57E-03 | 1.00 | GOLD |
| DLG4 | 1 | 0 | 12192 | 1 | 0 | 5237 | 2 | 0 | 3.77E-03 | 1.00 | ASD5 |
| SMC3 | 1 | 0 | 12192 | 1 | 1 | 5237 | 2 | 1 | 4.51E-03 | 0.19 | ASD4 |
| KMT2E | 0 | 0 | 12192 | 2 | 0 | 5237 | 2 | 0 | 7.16E-03 | 1.00 | ASD4 |
| PARD3B | 1 | 0 | 12192 | 1 | 0 | 5237 | 2 | 0 | 7.79E-03 | 1.00 | ASD5 |
| PTK7 | 1 | 0 | 12192 | 1 | 0 | 5237 | 2 | 0 | 9.99E-03 | 1.00 | ASD4 |
| SRCAP | 1 | 0 | 12192 | 1 | 0 | 5237 | 2 | 0 | 1.25E-02 | 1.00 | ASD4 |
| PHF2 | 0 | 0 | 12192 | 2 | 0 | 5237 | 2 | 0 | 1.60E-02 | 1.00 | ASD5 |
| ZC3H4 | 0 | 0 | 13407 | 2 | 0 | 5237 | 2 | 0 | 1.75E-02 | 1.00 | GOLD |
| SETD2 | 0 | 0 | 13407 | 2 | 0 | 5237 | 2 | 0 | 1.77E-02 | 1.00 | GOLD |
| DIP2A | 0 | 0 | 13407 | 2 | 0 | 5237 | 2 | 0 | 1.79E-02 | 1.00 | GOLD |
| UNC80 | 1 | 0 | 12192 | 1 | 0 | 5237 | 2 | 0 | 1.83E-02 | 1.00 | ASD5 |
| ZNF292 | 1 | 0 | 11731 | 1 | 0 | 5237 | 2 | 0 | 1.88E-02 | 1.00 | ASD6 |
| PHIP | 1 | 0 | 13407 | 1 | 0 | 5237 | 2 | 0 | 1.88E-02 | 1.00 | GOLD |
| WDFY3* | 0 | 0 | 12192 | 2 | 0 | 5237 | 2 | 0 | 1.93E-02 | 1.00 | ASD5 |
| PLXNB1 | 1 | 1 | 12192 | 1 | 0 | 5237 | 2 | 1 | 1.93E-02 | 0.40 | ASD5 |
| ASXL3 | 0 | 0 | 11731 | 2 | 0 | 5237 | 2 | 0 | 2.17E-02 | 1.00 | ASD6 |
| LAMC3 | 0 | 0 | 13407 | 2 | 0 | 5237 | 2 | 0 | 2.73E-02 | 1.00 | GOLD |
| DOCK8 | 1 | 0 | 11731 | 1 | 0 | 5237 | 2 | 0 | 5.40E-02 | 1.00 | ASD6 |
| KMT2C | 0 | 0 | 11731 | 2 | 0 | 5237 | 2 | 0 | 7.15E-02 | 1.00 | ASD6 |
| COL4A3BP | 0 | 0 | 13407 | 0 | 4 | 5237 | 0 | 4 | 1.00 | 1.75E-07 | GOLD |
| PPP2R5D | 0 | 0 | 13407 | 1 | 3 | 6158 | 1 | 3 | 1.40E-02 | 1.04E-06 | GOLD |
| TRIO | 0 | 1 | 13407 | 1 | 3 | 5237 | 1 | 4 | 0.18 | 1.44E-04 | GOLD |
| TBL1XR1 | 0 | 0 | 13407 | 1 | 2 | 6158 | 1 | 2 | 1.45E-02 | 6.37E-04 | GOLD |
| PTPN11 | 0 | 0 | 12192 | 0 | 2 | 5237 | 0 | 2 | 1.00 | 3.93E-03 | ASD4 |
| DLGAP1 | 0 | 1 | 12192 | 0 | 1 | 5237 | 0 | 2 | 1.00 | 5.10E-03 | ASD4 |
| TANC2 | 0 | 1 | 12192 | 1 | 1 | 5237 | 1 | 2 | 0.11 | 1.36E-02 | ASD5 |
| SRGAP3 | 0 | 1 | 12192 | 0 | 1 | 5237 | 0 | 2 | 1.00 | 1.47E-02 | ASD5 |
| ITPR1 | 0 | 1 | 11731 | 0 | 2 | 5237 | 0 | 3 | 1.00 | 1.80E-02 | ASD6 |
| ADCY5 | 0 | 0 | 12192 | 0 | 2 | 5237 | 0 | 2 | 1.00 | 1.94E-02 | ASD5 |
*
An LGD variant was identified in this gene using previously published smMIPs; therefore, the LGD count differs compared to Supplementary Table 11 to avoid duplicate counting.
α
FDR corrections were based on the number of samples for which parental DNA could be tested.