Table 1.
Potentially pathogenic variants in known ASD and neurodevelopmental disease genes identified in affected individuals from the East African ASD cohort
| Affected individual | Inheritance | Variant(s) | Variant type | Gene(s) | Variant location | Mutation | Relevant OMIM or G2PDD phenotype | SFARI score | pLI score | LOEUF score |
|---|---|---|---|---|---|---|---|---|---|---|
| MCD-01-4 | inherited homozygous (ROH) | chr7:91,321,289:C:A | SNV | FZD1, MTERF1, AKAP9 | enhancer | – | – | 2 (AKAP9) | 0.04; 0; 0 | 0.60; 1.26; 0.40 |
| MCD-02-3 | X-linked | chrX:135,960,149:G:A | missense | RBMX | exonic | p.P105S | intellectual disability (XLR) | – | 0.83 | 0.43 |
| MCD-04-5 | inherited homozygous (ROH) | chr12:116,591,972:C:G; chr12:116,592,155:T:A; chr12:116,714,156:T:C | SNV | MED13L | enhancer, promoter | – | impaired intellectual development (AD) | 1 | 1 | 0.06 |
| MCD-04-5 | inherited homozygous (ROH) | chr7:98,477,886:T:- | Indel | TRRAP | promoter | – | developmental delay (AD) | 2S | 1 | 0.06 |
| MCD-05-3 | compound heterozygous | chr17:78,078,662:G:A; chr17:78,083,769:C:G | missense | GAA | exonic | p.A93T; p.P451R | glycogen storage disease II (AR) | – | 0 | 0.98 |
| MCD-05-3 | inherited homozygous | chr10:114,849,211:C:A | missense | TCF7L2 | exonic | p.P179H | TCF7L2-related neurodevelopmental disorder | 1 | 1 | 0.27 |
| MCD-07-3 | inherited homozygous (ROH) | chr16:71,062,908:A:C | SNV | HYDIN, VAC14 | enhancer | – | ciliary dyskinesia (AR) (HYDIN); striatonigral degeneration (AR), progressive neurological disorder and regression (VAC14) | 2 (HYDIN) | 0; 0.19 | 0.51; 0.42 |
| MCD-07-3 | compound heterozygous | chr17:78,081,608:A:G; chr17:78,086,394:G:A | missense | GAA | exonic | p.N290D; p.R591Q | glycogen storage disease II (AR) | – | 0 | 0.98 |
| MCD-08-3∗ | De novo | chr6:170,597,575:T:C | missense | DLL1 | exonic | p.E141G | neurodevelopmental disorder (AD) | 2S | 1 | 0.10 |
| MCD-08-3∗ | De novo | chr8:61,757,960:C:A | missense | CHD7 | exonic | p.H1734Q | CHARGE syndrome (AD) | 1 | 1 | 0.08 |
| MCD-08-3∗ | De novo | chr5:140,308,275:.:T | Frameshift | PCDHAC1 | exonic | p.S601Lfs∗4 | – | 2 | 0 | 1.02 |
| MCD-08-3∗ | De novo | chr12:57,570,830:C:T | missense | LRP1 | exonic | p.T1333I | – | 2 | 1 | 0.06 |
| MCD-13-3 | inherited homozygous (ROH) | chr12:112,927,353:C:T | SNV | PTPN11 | enhancer | – | LEOPARD syndrome (AD) | 1 | 1 | 0.14 |
| MCD-13-3 | X-linked | chrX:77,245,178:A:T | missense | ATP7A | exonic | p.T354S | Menkes disease (XLR) | – | 1 | 0.22 |
| MCD-15-3 | compound heterozygous | chr8:2,886,901:G:A; chr8:3,087,702:C:T | missense | CSMD1 | exonic | p.L2599F; p.R1402H | – | 2 | 1 | 0.21 |
| MCD-15-3 | compound heterozygous | chr8:17,815,232:T:C; chr8:17,830,089:C:G | missense | PCM1 | exonic | p.M663T; p.T1279R | – | 2 | 0 | 0.58 |
| MCD-16-3 | compound heterozygous | chr12:2,794,928:G:A; chr12:2,797,853:C:T | missense | CACNA1C | exonic | p.R1875Q; p.R2017W | Timothy syndrome (AD) | 1 | 1 | 0.10 |
| MCD-17-3 | compound heterozygous | chr5:89,923,448:G:T; chr5:89,949,452:A:T; chr5:90,368,293:T:C | missense | ADGRV1 | exonic | p.D365Y; p.N1354I; p.L6061S | Usher syndrome (AR) | – | 0 | 0.52 |
| MCD-17-3 | inherited homozygous (ROH) | chr1:154,842,199:-:GCTGCT | indel | KCNN3 | promoter | – | Zimmermann-Laband syndrome 3 (AD) | – | 0.97 | 0.32 |
| MCD-18-3 | compound heterozygous | chr1:215,901,460:C:T; chr1:215,933,087:G:T | missense | USH2A | exonic | p.G3993D; p.Q3716K | Usher syndrome (AR) | 2 | 0 | 0.86 |
| MCD-18-3 | inherited homozygous | chr7:4,830,879:G:A | missense | AP5Z1 | exonic | p.V763M | spastic paraplegia (AR) | – | 0 | 1.47 |
| MCD-19-3 | compound heterozygous | chr18:50,432,527:A:G; chr18:51,013,227:C:T | missense | DCC | exonic | p.N176D; p.P1266L | developmental split-brain syndrome (AR); Mirror movements 1 (AD) | 2 | 0.99 | 0.28 |
| MCD-19-3 | compound heterozygous | chr18:72,775,399:G:A; chr18:72,776,411:T:C | missense | ZNF407 | exonic | p.D1908N; p.L2245P | SIMHA syndrome (AR) | – | 1 | 0.09 |
| MCD-19-3 | inherited homozygous (ROH) | chr3:123,168,229:C:A | SNV | ADCY5 | promoter | – | neurodevelopmental disorder with dyskinesia (AD or AR) | 2 | 1 | 0.25 |
| MCD-20-3, MCD-20-4 | inherited homozygous (ROH) | chr16:67,596,146:G:A | SNV | CTCF | promoter | – | intellectual development disorder (AD) | 1 | 1 | 0.15 |
| MCD-22-3 | inherited homozygous | chr10:73,485,206:C:T | missense | CDH23 | exonic | p.R1170W | Usher syndrome (AR) | – | 0 | 0.57 |
| MCD-24-3 | compound heterozygous | chr4:187,538,263:T:A; chr4:187,629,414:T:C | missense | FAT1 | exonic | p.N2991Y; p.E523G | – | 2 | 0 | 0.43 |
| MCD-25-3 | inherited homozygous (ROH) | chr2:25,140,835:G:A; chr2:25,142,282:C:T | SNV | ADCY3 | promoter | – | – | 2 | 0 | 0.68 |
| MCD-33-4 | compound heterozygous | chr5:150,886,883:G:T; chr5:150,901,082:C:T | missense | FAT2 | exonic | p.P4117T; p.G3691E | spinocerebellar ataxia (AD) | – | 0 | 0.51 |
| MCD-33-4 | X-linked | chrX:147,027,118:A:G | missense | FMR1 | exonic | p.Q462R | fragile X syndrome (XLR) | 1 | 0.65 | 0.42 |
List of deleterious coding and brain-specific regulatory noncoding variants affecting known ASD or neurodevelopmental disease genes identified for each affected individual. ROH indicates inherited homozygous variants that are within runs of homozygosity. For SFARI score, S denotes syndromic genes. AD, autosomal dominant; AR, autosomal recessive; indel, insertion or deletion; LOEUF, loss-of-function observed/expected upper bound fraction; SNV, single nucleotide variant; XLR, X-linked recessive. ∗Sample with a missing parent sample where compound heterozygous variant calling was not possible and de novo, inherited homozygous, and X-linked variant calling relied on one parent only.