Fig. 2: Prevalence of DDX/DHX variants in hematological neoplasia and summary of DHX40 variants in colorectal and hematological neoplasia.

A, B Germline exomes (fibroblasts) from our hospital-based hematological series. Variant selection criteria were the same as for FCCTX, except that in silico evaluations were based on five programs instead of six. Bar chart in 3B includes DDX/DHX genes affected by at least one variant. See Supplementary Table 5 for variant details. C, D Somatic exomes (leukemic bone marrow) from our hospital-based hematological series. Nonsynonymous variants with allele frequency (VAF) 1% or higher and somatic p value < 0.01 by VarScan2 were selected. The “other/combined” group in 3C consists of mainly combined diagnoses of different hematological lineages. The four cases of somatic DHX40 variants listed in 3C include p.S210*, VAF 7% (AML_3 with recurrent AML); p.Y468F, VAF 7% (AML_43 with polycythemia vera and subsequent acute promyelocytic leukemia); p.D474Y, VAF 7% (MM_14 with multiple myeloma); and p.E121*, VAF 37% (MM_20 with recurrent multiple myeloma). Bar chart in 3D includes DDX/DHX genes affected by at least one variant. See Supplementary Table 6 for variant details. E Lollipop diagram of germline (triangle) and somatic (circle) variants in DHX40 present in colorectal, myeloid, and lymphoid neoplasia. Variants shown in red font are reported in this article, and variants in black are from publicly available datasets in cBioPortal (see Supplementary Materials and Methods). The germline variant p.V237Efs comprised both colorectal and myeloid/lymphoid phenotypes (Fig. 1A). See legend for Fig. 1A for functional domains of DHX40 (the corresponding exons of DHX40 are underneath the diagram).