Diagram of the workflow and a high-level summary of variants analyzed. (A) Visual depiction of project workflow showing the selection and filtering steps adopted to generate the catalog of BTPD variants used in the MDT review and the statistical analysis of UKB exome data set (“Methods”); from left to right: the online sources used to retrieve gene and variant information; the number of UKB participants available for inclusion in the study; the number of BTPD variants and the number of UKB participants carrying a BTPD variant; review of BTPD variants for pathogenicity by MDTs and used for association analysis to estimate effect sizes and ORs. Of the 967 BTPD variants, 213 (22%) had sufficient UKB carriers to perform an association analysis (“Methods”). Altogether, we estimated effect sizes for 128 variants in platelet disorder DGGs associated with platelet count and volume, ORs for 67 of these variants and for 61 variants in the coagulation genes F8/F9/VWF on bleeding, and ORs for 24 variants in thrombotic disorder genes PROC/PROS1/SERPINC1 on VTE (supplemental Table 4). (B) Venn diagram showing the overlap for variant pathogenicity labels between the resources with ClinVar (orange), HGMD (yellow), and NIHR BioResource (green). (C) VEP-calculated functional impacts of the 299 606 pathogenic and likely pathogenic variants, subclassified according to whether they were observed or not in the UKB study population. x-axis: variants grouped according to their impact on protein function (“Methods”), ranging from low (eg, synonymous single nucleotide variants [SNV]), modifier, moderate to high impact (eg, premature stop). y-axis: number of unique variants in each functional effect category. In gray are the variants not observed in UKB, and in blue those observed. (D) CADD (PHRED) scores for the pathogenic and likely pathogenic variants: CADD score distribution for all cataloged-variants in gray and for the subset observed in UKB participants in blue. y-axis: relative density.