Table 2 Rare loss-of-function variants in intolerant genes identified in ten singleton cases with CAS
Proband | Chr | Base | Gene | Transcript | cDNA change | Protein change | Impact | RVIS | pLI | Phenotype previously associated with LoF | Classification |
|---|---|---|---|---|---|---|---|---|---|---|---|
10 | 8 | 41806856 | KAT6A | ENST00000265713 | c.1599-56_1621del | p.? | Splice acceptor variant | 3 | 1.00 | Developmental delay, language delay, hypotonia, specific facial features [45] | Pathogenic |
13 | 18 | 42531084 | SETBP1 | ENST00000282030 | c.1781del | p.P594Lfs*36 | Frameshift | 10 | 1.00 | Developmental delay and language delay [46] | Pathogenic |
3 | 193380725 | OPA1 | ENST00000361908 | c.2581C>T | p.R861* | Stop gained | 10 | 0.99 | Dominant optic atrophy | VUS | |
1 | 21923758 | RAP1GAP | ENST00000542643 | c.*35-1G>A | p.? | Splice acceptor variant | 18 | 0.97 | NA | VUS | |
14 | 8 | 77761747 | ZFHX4 | ENST00000521891 | c.3646-1G>A | p.? | Splice acceptor variant | 1 | 1.00 | Developmental delay and specific facial features (gene deletions only) [48] | Pathogenic |
15 | 22 | 40662274 | TNRC6B | ENST00000454349 | c.2040G>A | p.W680* | Stop gained | 3 | 1.00 | Autism spectrum disorder [47] | Pathogenic |
18 | 16 | 14234400 | MKL2 | ENST00000571589 | c.-63-1G>C | p.? | Splice acceptor variant | 3 | 1.00 | NA | Likely pathogenic |
