Mutations detected in CVID patients include genes associated with impaired B-cell development (e.g., IKZF1, BAFFR, TWEAK, CD27, STAT1 GOF, NFKB2, IRF2BP2), impaired CSR/SHM (e.g., BACH2, IL21, IL21R), excessive lymphoproliferation (e.g., CTLA4, LRBA, PIK3CD, STAT3 GOF), and impaired B-cell activation and tolerance (e.g., NFKB1, TACI, CD19, CD21, ICOS, BLK, PLCG2, CD81, CD20) [88,135,138,139]. The gene discussed is ICOS; the disease is common variable immunodeficiency.