Table 2 Potentially causative pathogenic variants derived from screening of 144 Saudi epilepsy subjects. Chromosomal position is outlined for the 32 putative pathogenic variants in 30 gene regions along with annotation of the putative pathogenic variant mapped to human reference genome build 37 (GRCh37). Minor allele frequencies (MAF) are shown for the: Saudi epilepsy cohort; Genome Aggregation Database (GnomAD); and Human Gene Mutation Database (HGMD). ClinVar annotation for likely clinical significance is also listed
Chromosome position | Patient(s) with Heterozygous or Homozygous** Variant | Variant Type | Gene (NCBI Gene ID) | Cohort Variant MAF* | ExAC MAF | GnomAD MAF | HGMD Mutation Phenotype | Clinical significance in CLINVAR database |
|---|---|---|---|---|---|---|---|---|
chr1: 43907014 | 065 | Missense | SZT2 | 0.003 | 0.00034 | 0.002581 | Epileptic encephalopathy early-onset | Conflicting interpretations of pathogenicity |
chr1: 47746675 | 094, 128, 134 | Missense | STIL | 0.01 | 0.00213 | 0.003538 | Intellectual disability seizures microcephaly | Conflicting interpretations of pathogenicity |
chr1: 97915614 | 101, 141 | Splicing | DPYD | 0.007 | 0.007067 | Dihydropyrimidine dehydrogenase deficiency | drug response | |
chr1: 119683231 | 070, 129, 135 | Missense | WARS2 | 0.01 | 0.006159 | Intellectual disability | Conflicting interpretations of pathogenicity | |
chr1: 160011671 | 021, 045 | Missense | KCNJ10 | 0.007 | 0.001179 | Developmental delay failure to thrive ataxia hypotonia and tonic–clonic seizures | Uncertain significance | |
chr2: 166243269 | 019 | Missense | SCN2A | 0.003 | 0.00073 | 0.005002 | Epileptic encephalopathy | Conflicting interpretations of pathogenicity |
chr2: 166848930 | 069 | Missense | SCN1A | 0.003 | 0.00056 | 0.004116 | Intractable epilepsy | Conflicting interpretations of pathogenicity |
chr2: 167138296 | 085 | Missense | SCN9A | 0.003 | 0.00189 | 0.008274 | Febrile seizures | Conflicting interpretations of pathogenicity |
chr3: 38739016 | 007, 039 | Frame shift | SCN10A | 0.007 | 0.0001 | 0.000130 | Refractory epilepsy & autism spectrum disorder | Uncertain significance |
chr3: 132378559 | 009, 101 | Stop gained | UBA5 | 0.007 | 0.009118 | Pathogenic | ||
chr4: 119736287 | 032, 141 | Missense | SEC24D | 0.007 | Not seen | Intellectual disability and epilepsy | Likely pathogenic | |
chr8: 1719594 | 071 | Missense | CLN8 | 0.003 | 0.00082 | 0.002221 | Neuronal ceroid lipofuscinosis late infantile | Conflicting interpretations of pathogenicity |
chr10: 79396648 | 017** | Stop gain | KCNMA1 | 0.008 | Not seen | Epilepsy | ||
chr11: 9225637 | 047 | Frame shift | DENND5A | 0.003 | Not seen | Epileptic encephalopathy | Pathogenic | |
chr11: 93521218 | 087 | Missense | MED17 | 0.003 | 0.000115 | Seizures and hypoplasia of the corpus callosum | Uncertain significance | |
chr12: 42863325 | 083 | Missense | PRICKLE1 | 0.003 | 1.00E−05 | 0.000641 | Progressive myoclonus epilepsy-ataxia syndrome | Likely pathogenic |
chr12: 52164462 | 096 | Missense | SCN8A | 0.003 | 1.00E−05 | 0.000109 | Paroxysmal kinesigenic dyskinesia | Conflicting interpretations of pathogenicity |
chr12: 111856571 | 021, 037, 043, 138 | Missense | SH2B3 | 0.014 | 0.00099 | 0.004796 | Erythrocytosis idiopathic | Uncertain significance |
chr13: 100925464 | 048 | Missense | PCCA | 0.003 | 0.000976 | Epilepsy & neurodevelopmental delay | Conflicting interpretations of pathogenicity | |
chr15: 23006299 | 002, 009, 040, 044, 050, 057, 089 | In-frame insertion | NIPA2 | 0.024 | 0.008426 | Childhood absence epilepsy | ||
chr15: 52632432 | 121 | Missense | MYO5A | 0.003 | Not seen | Developmental delay seizures & dystonia | Pathogenic | |
chr15: 73617728 | 127 | Missense | HCN4 | 0.003 | 0.000018 | Myoclonic epilepsy benign infantile | ||
chr15: 89866693 | 049 | Missense | POLG | 0.003 | 0.00036 | 0.001169 | Depression ataxia and cardiomyopathy | Conflicting interpretations of pathogenicity |
chr15: 89870429 | 030 | Missense | POLG | 0.003 | 0.00044 | 0.002358 | Progressive external ophthalmoplegia | Conflicting interpretations of pathogenicity |
chr15: 89876827 | 032 | In-frame insertion | POLG | 0.003 | 0.004516 | Hepatic encephalopathy | Benign/Likely benign | |
chr16: 150392 | 112 | Missense | NPRL3 | 0.003 | 0.000933 | Focal epilepsy | Uncertain significance | |
chr16: 28500627 | 104 | Missense | CLN3 | 0.003 | 4.00E−05 | 0.000203 | Retinal degeneration | Uncertain significance |
chr17: 61791402 | 084 | Missense | STRADA | 0.003 | Not seen | Pathogenic | ||
chr19: 14024452 | 071 | Splicing | CC2D1A | 0.003 | Not seen | Autism spectrum disorder intellectual disability and seizures | Pathogenic | |
chr20: 61981924 | 055, 098, 106, 121 | Missense | CHRNA4 | 0.014 | Not seen | Epilepsy nocturnal frontal lobe | Pathogenic | |
chr21: 34003387 | 141 | Missense | SYNJ1 | 0.003 | 0.00082 | 0.008603 | Parkinson disease | Likely benign |
chr22: 32188751 | 019 | Stop gained | DEPDC5 | 0.003 | Not seen | Epilepsy familial focal with variable foci | Pathogenic |