We adopted a multi-pronged analysis approach involving scrutiny of a virtual germline panel of 756 genes known to cause immune deficiency, autoinflammation and vasculitis [33, 34]; Exomiser analysis using HPO terms to aid variant prioritization across the whole exome [28]; somatic variant gene panel analysis of six preselected genes (NLRC4, NLRP3, NOD2, STING1, TNFRSF1A, UBA1) known to be associated with disease states when present as somatic variants [35–42]; and read count CNV analysis [26]. The gene discussed is NOD2; the disease is Immunodeficiency.