Panel A shows pedigree diagrams of Kindred A and Kindred B families with affected and carrier individuals identified by genotype labels. Panel B shows DNA sequencing chromatograms from healthy control, 2.1 P1, 2.2 P2, and 1.2, highlighting variant positions with arrows. Panel C shows DNA sequencing chromatograms comparing healthy control and P3, demonstrating sequence variation at the mutation site. Panel D shows a scatter plot of Combined Annotation Dependent Depletion score versus minor allele frequency with MSC cutoff 10 indicated. Panel E shows a gene and protein domain schematic displaying exons, domains, deletions, and annotated mutation positions.
Novel STAT2 variants in two kindreds. (A) Pedigrees of two unrelated kindreds with STAT2 variants. Double lines connecting parents indicate consanguinity. Filled symbols indicate individuals with homozygous mutations, and half-filled symbols indicate carriers of heterozygous mutations. E? indicates unknown genotype. (B) Sanger sequencing results for c.1467_1468insC in an unrelated healthy control (HC), a related carrier (I.2), P1 (II.1), and P2 (II.2). (C) Sanger sequencing results for cDNA of the beginning of exon 10 of an unrelated healthy control (HC) and P3. (D) Population genetics of two novel STAT2 variants compared to homozygous coding missense STAT2 mutations from gnomAD and known pathogenic variants from the literature. Green: gnomAD variants predicted benign; orange: gnomAD variants of uncertain significance; black: eight previously reported pathogenic biallelic STAT2 variants; red: novel STAT2 variants K490Qfs*41 and c.941+ 1G>T. MAF, minor allele frequency; MSC, mutation significance cutoff. (E) Schematic illustration of the STAT2 gene and the STAT2 protein with its domains. Previously reported STAT2 variants are indicated in black, novel variants in red. N, N-terminal domain; CC, coiled domain; DBD, DNA-binding domain; L, linker domain; SH2, Scr homology two domain; P-Y690, tyrosine phosphorylation site; TAD, transcriptional activation domain.