Bioinformatics: Variant calling
Variants were called using Clair v2 (Luo et al., 2020) and filter parameters for variants required >20x coverage, allele frequency 20-80%, 96% confidence, and allele agreement with the validated DNM. The remaining variants were error polished using the high base accurate WES data, removing variants that disagree with any overlapping WES data. WES data for patients and parents was used in filtering ONT called variants illustrated in Figure 2 and Supplementary Tables 4 and 5. Intronic variants identified were further error polished where the inheritance information was available from long-read parental data.