Table 2.
Pathogenic, likely pathogenic, and variants of uncertain significance in individuals with PNES.
| ID | Variant type | Gene/s | Associated neurological/psychiatric disorder | ACMG-AMP classification | CytoBand | Chr | Start GRCh37 | Stop GRCh37 | Consequence/nucleotide change/affected exon | Mis_z | pLI |
|---|---|---|---|---|---|---|---|---|---|---|---|
| PNES1 | 1.58 Mb deletion | 7 genes | Epilepsy | Pathogenic | 10q23.1-q23.2 | 10 | 87,136,787 | 88,718,934 | CN loss | – | – |
| PNES2 | 218 Kb deletion | 9 genes | Epilepsy | Pathogenic | distal 16p11.2 | 16 | 28,826,049 | 29,044,745 | CN loss | – | – |
| PNES3 | 229 Kb deletion | PAFAH1B1, METTL16 | Epilepsy | Pathogenic | 17p13.3 | 17 | 2,341,350 | 2,570,479 | CN loss | – | – |
| PNES4 | Nonsynonymous SNV | NSD1 | Neurological/psychiatric | Likely pathogenic | 5q35.3 | 5 | 176,720,953 | 176,720,953 | p.Lys1926Arg (exon 23 out of 23) | 3.70 | 1.00 |
| PNES5 | 4.91 Mb Deletion | 39 genes | Neurological/psychiatric | Pathogenic | 10q11.22-q11.23 | 10 | 46,943,377 | 51,856,375 | CN loss | – | – |
| PNES6 | Nonsynonymous SNV | GABRA5 | Neurological/psychiatric | Likely pathogenic | 15q12 | 15 | 27,188,485 | 27,188,485 | p.Ala334Gly (exon 10 out of 11) | 3.31 | 0.88 |
| PNES7 | Stopgain SNV | LHX9 | NA | Uncertain significance | 1q31.3 | 1 | 197,896,819 | 197,896,819 | p.Gln269Ter (exon 4 out of 5)a | 1.13 | 0.98 |
| PNES8 | Nonsynonymous SNV | MAPKAPK2 | NA | Uncertain significance | 1q32.1 | 1 | 206,904,045 | 206,904,045 | p.Leu235Pro (exon 6 out of 10) | 3.10 | 1.00 |
| PNES9 | Splicing SNV | CAMKV | NA | Uncertain significance | 3p21.31 | 3 | 49,899,726 | 49,899,726 | c.95+1G>A (exon 2 out of 11) | 3.39 | 1.00 |
| PNES10 | Stopgain SNV | GAPVD1 | NA | Uncertain significance | 9q33.3 | 9 | 128,118,066 | 128,118,066 | p.Arg1319Ter (exon 25 out of 28) b | 2.75 | 1.00 |
| PNES11 | Nonsynonymous SNV | PRPF8 | NA | Uncertain significance | 17p13.3 | 17 | 1,579,337 | 1,579,337 | p.Arg855Pro (exon 18 out of 43) | 8.55 | 1.00 |
| PNES12 | Splicing SNV | MYH9 | NA | Uncertain significance | 22q12.3 | 22 | 36,717,867 | 36,717,867 | c.706-1G>C (exon 7 out of 41) | 3.67 | 1.00 |
Chr: chromosome, GRCh37: Genome Reference Consortium Human Build 37, Mis_z: Z-score for missense variant intolerance of a gene, pLI: probability for the loss-of-function variant intolerance of a gene, Mb: mega base pairs, Kb: kilo base pairs, CN: copy number.
aExon numbers based on transcript NM_020204.
bExon numbers based on transcript NM_001282680.