Table 2.
Recurrent disruptive mutations in ID and ASD
| Genea,b | ID cases | ASD cases | Summaryc,d,e | ESP samples | |
|---|---|---|---|---|---|
| Variants | Frequency | ||||
| CHD8 | – | 9/2446 | 2 (O), 7 (O*) [+3 (N*)] | 0 | 0/6503 |
| SCN2A | 3/151 | 2/593 | 1 (L), 2 (R), 2 (S) [+1 (N*)] | 1 | 7/6503 |
| SYNGAP1 | 3/151 | – | 1 (L), 2 (R) | 1 | 207/6503f |
| GRIN2B | – | 3/2446 | 1 (O), 2 (O*) | 0 | 0/6503 |
| DYRK1A | – | 3/2446 | 1 (I), 1 (O), 1 (O*) | 0 | 0/6503 |
| ZNF292 | 1/151 | 1/593 | 1 (L), 1 (N) | 1 | 2/6503 |
| POGZ | – | 2/593 | 1 (I), 1 (N) | 1 | 1/6503 |
| KATNAL2 | – | 2/593 | 1 (O), 1 (S) | 1 | 1/6503 |
| TBR1 | – | 2/2446 | 1 (O), 1 (O*) | 0 | 0/6503 |
| CTNNB1 | 1/151 | 1/2446 | 1 (L), 1 (O*), [+1 (L*)] | 0 | 0/6503 |
| SETBP1 | 1/151 | 1/593 | 1 (O), 1 (R) | 3 | 58/6503f |
| ADNP | – | 2/2446 | 1 (O), 1 (O*) | 1 | 1/6500 |
| LRP2 | 1/151 | 1/593 | 1 (I), 1 (L) | 6 | 53/6500 |
| ARID1B | – | 2/2446 | 1 (O), 1 (O*) | 5 | 314/6500 |
Genes with two or more de novo truncating mutations observed in studies of ASD or ID are listed.
Additional abbreviations: KATNAL2, katanin p60 subunit A-like 2; LRP2, low density lipoprotein receptor-related protein 2; POGZ, pogo transposable element with ZNF domain; ZNF292, zinc finger protein 292.
The summary indicates studies in which mutations were discovered.
I, Iossifov et al. [26]; L, de Ligt et al. [28]; N, Neal et al. [25], O and O*: O’Roak et al. [24,44]; R, Rauch et al. [29]; S, Sanders et al. [27].
Mutations found in secondary replication screens or case-control studies are indicated in [brackets] with starred (*) reference. Truncating events found in the Exome Sequencing Project (ESP) database and their population frequencies are shown.
The truncating variants found in the ESP database in SYNGAP1 and SETBP1 genes fell at the extreme 3′ end of the gene, suggesting that they do not adversely affect gene function