By systematic search for fully penetrant, rare, non-synonymous, and LoF variants in exonic regions, we identified 12 potentially causal variants including two novel variants in known PID genes: X-linked agammaglobulinemia due to a novel BTK mutation and ICF immunodeficiency syndrome due to a novel DNMT3B mutation. Here, DNMT3B is linked to isolated agammaglobulinemia.