Monoallelic variants in genes associated with autosomal dominant PIDs, identified in patients with rheumatic diseases with persistent hypogammaglobulinaemia and those without
| Pat. ID | Gene | Ref. seq. transcript | Coding change | Protein change | gnomAD allele freq. | RS-ID | CADD score | MSC–CADD score | PolyPhen2 score | PolyPhen2 pred. | SIFT score | SIFT pred. |
| A: Patients with persistent hypogammaglobulinaemia | ||||||||||||
| 4 | NFKB1 | NM_001165412.ex.15 | c.1601G>A | p.R534H | 0.0004455 | RS150281816 | 29.000 | 3.313 | 0.960 | Probably damaging | 0.000 | D |
| 14 | PIK3CD | NM_005026.ex.22 | c.2799C>A | p.H909Q | – | – | 28.500 | 23.800 | 0.995 | Probably damaging | 0.000 | D |
| 25 | PTEN | NM_001304718.ex.8 | c.1021T>G | p.F341V | – | – | 27.900 | 2.182 | 0.998 | Probably damaging | NA | NA |
| 29 | NFKB1 | NM_001165412.ex.24 | c.2793G>C | p.E930D | – | – | 23.800 | 3.313 | 0.990 | Probably damaging | 0.000 | D |
| 33 | NFKB1 | NM_003998.ex.10 | c.865G>T | p.E289* | – | – | 41.000 | 3.313 | NA | NA | 0.000 | D |
| 42 | NFKBIA | NM_020529.ex.5 | c.682C>T | Q228* | – | – | 39.000 | 24.800 | NA | NA | 0.040 | D |
| 57 | NFKB1 | NM_003998.ex.16 | c.1736G>A | p.R579K | 0.001 | RS4648086 | 18.740 | 3.313 | 0.911 | Probably damaging | 0.830 | T |
| 59 | STAT3 | NM_003151.ex.22 | c.2144C>T | p.T715M | – | – | 21.400 | 15.29 | 0.719 | Possibly damaging | 0.100 | T |
| 60 | IRF2BP2 | NM_181524.ex.5 | c.1282C>A | p.L428M | – | – | 24.000 | 3.313 | 0.999 | Probably damaging | 0.090 | T |
| 62 | NFKB1 | NM_003998.ex.10 | c.865G>T | p.E289* | – | – | 41.000 | 3.313 | NA | NA | 0.000 | D |
| B: Patients without hypogammaglobulinaemia | ||||||||||||
| 121 | IRF2BP2 | NM_001077397.ex.1 | c.958C>A | p.P320T | – | – | 23.600 | 3.313 | 0.961 | Probably damaging | 0.010 | D |
*substitution - nonsense.
*, substitution-nonsense; CADD, Combined Annotation Dependent Depletion; D, damaging; freq., frequency; gnomAD, Genome Aggregation Database; Pat. ID, patient identification number; MSC, Mutation Significance Cut-off; NA, not applicable; PIDs, primary immunodeficiency disorders; PolyPhen2, Polymorphism Phenotyping v2; pred., prediction; ref. seq., reference sequence; RS-ID, reference-single nucleotide polymorphism identity number; SIFT, Sorting Intolerance From Tolerance; T, tolerated.