Table 3.
Distribution of reclassified variant observations across IUIS categories
| IUIS category | Genes n |
Total variants n | P/LP n (%)* | VUS n (%)* | Novel n | Genes identified |
|---|---|---|---|---|---|---|
| Immunodeficiencies affecting cellular and humoral immunity | 11 | 34 | 22 (64.7) | 9 (26.5) | 5 | IL2RG, JAK3, CD3D, RAG1/2, DCLRE1C, ADA, CD40LG, ZAP70, DOCK8, MAP3K14 |
| CID with associated or syndromic features | 18 | 52 | 23 (44.2) | 12 (23.1) | 6 | WAS, ATM, BLM, PMS2, RECQL4, DiGeorge, CHD7, STAT3, SPINK5, IKBKB, STIM1, PNP, SP110, BCL11B, NFE2L2, STAT5B, KMT2A, KMT2D |
| Predominantly Antibody Deficiencies | 9 | 10 | 3 (30.0) | 2 (20.0) | 1 | BTK, PIK3CD, PTEN, TRNT1, NFKB2, IKZF1, AICDA, MSH6, CARD11 |
| Diseases of Immune Dysregulation | 17 | 40 | 12 (30.0) | 12 (30.0) | 6 | PRF1, UNC13D, STX11, STXP2, LYST, RAB27A, CTLA4, LRBA, DEF6, STAT3, IKZF1, PEPD, TLR7, NCKAP1L, SH2D1A, XIAP, MAGT1 |
| Congenital defects of phagocyte number or function | 12 | 30 | 20 (66.7) | 3 (10.0) | 4 | ELANE, GFI1, VPS13B, CSF3R, SMARCD2, FERMT3, ACTB, CFTR, CYBB, NCF1/4, G6PD |
| Defects in Intrinsic and Innate Immunity | 11 | 14 | 6 (42.9) | 5 (35.7) | 3 | IFNGR1, CYBB, IRF8/9, TYK2, RORC, STAT1, POLR3A, MYD88, TLR7, GATA2 |
| Autoinflammatory Disorders | 16 | 40 | 8 (20.0) | 5 (12.5) | 2 | ADA2, TREX1, RNASEH2A, DNASE1L3, RELA, MEFV, MVK, NLRP1/3/12, LPIN2, TNFRSF1A, NOD2, CARD14, PSMB8, TNFAIP3 |
| Complement Deficiencies | 4 | 7 | 4 (57.1) | 1 (14.3) | 0 | C3, C8B, SERPING1, CFD |
| Bone Marrow Failure | 9 | 18 | 9 (50.0) | 5 (27.8) | 4 | BRCA1/2, FANCG, FANCI, PALB2, SLX4, TERT, RTEL1, PARN, TP53 |
This table summarizes reported IEI-related variant observations across IUIS disease categories after systematic reclassification. Gene counts indicate the number of distinct genes per category, while variant counts indicate reported variant observations. Percentages for P/LP and VUS variants were calculated using the total number of variants in each category as the denominator. Novel variants were defined as variants absent from both ClinVar and HGMD