Figure 2.
Panel A: A flowchart of the applied variant filtering process. Called variants are filtered through three steps: reported pathogenic or likely pathogenic variants with an allele frequency of 0.5 or less, truncating and frameshift variants with an allele frequency of 0.001 or less, and additional variants with an allele frequency of 0.0005 or less. Filtered variants are then reviewed, excluding one heterozygous variant in a gene with autosomal recessive inheritance. Variants marked for manual review are identified. Panel B: A flowchart of the variant reporting strategy. Variants marked for manual review are categorized into autosomal dominant, autosomal recessive, X-linked, and autosomal recessive/X-linked disorders. Each category has specific criteria for identifying positive cases, including the 1 or 2 times presence of heterozygous, homozygous, or hemi/homozygous pathogenic or likely pathogenic variants, and variants of uncertain significance in the same gene. Positive cases are identified.
Variant filtering and reporting. (A and B) Flowcharts of the (A) applied variant filtering and (B) variant reporting strategy. A detailed overview of the applied filters is provided in Table S2. Heterozygous pathogenic (P) or likely pathogenic (LP) variants in genes with AR and XL inheritance were only reported when an additional VUS was identified, as indicated by the dashed box (B). AD, autosomal dominant.