Fig. 2: In silico sequence- and structure-based analysis of variants in candidate genes.
From: Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR
a Variants in DYRK1A from our mega-analysis (n = 10) compared to public databases, including (likely) pathogenic (n = 24) and (likely) benign variants (n = 52) from ClinVar, and gnomAD (n = 287), across different predictors of deleteriousness (CADD_PHRED, p = 0.227, p < 0.002, p = 0.009, respectively; EVE, p = 0.103, p = 0.0011, p = 0.24, respectively; REVEL, p = 0.16, p < 0.0001, p < 0.0001, respectively) and by their distribution in missense-intolerant regions (MTR, p = 0.076, p < 0.0001, p = 0.00016, respectively). Paired one-sided Wilcoxon test: ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, ns: p > 0.05. b Variants in EGFR from our mega-analysis (n = 17) compared to public databases including (likely) pathogenic (n = 29) and (likely) benign variants (n = 10) from ClinVar, and gnomAD (n = 604), across different predictors of deleteriousness (CADD_PHRED, p = 0.003, p < 0.0001, p < 0.0001, respectively; EVE, p = 0.838, p = 0.00021, p < 0.0001, respectively; REVEL, p = 0.406, p = 0.00015, p < 0.0001, respectively) and by their distribution in missense-intolerant regions (MTR, p = 0.03, p = 003, p < 0.0001, respectively). Paired one-sided Wilcoxon test: ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, ns: p > 0.05. Data are presented as box plots that indicate median (center), and the interquartile range (IQR; bounds of box) up to 1.5 IQR (whiskers). Adjustments for multiple testing were done with the Holm-Bonferroni method. c Variants in DYRK1A mapped on the Dyrk1A structure (PDB-ID: 7FHS – chain A). Essential-3D sites are shown in pink. d Variants in EGFR mapped on protein structure fragments of the epidermal growth factor receptor (EGFR). *Variants observed in multiple samples across our cohorts. †Variants present in COSMIC at significance tiers 1–3.
