TABLE 2.
List of variants of auto‐inflammatory disorders genes found in FMF patients
| Gene | Variant details | Chr: position | Type of Mutation | dbSNP ID | Cases (N) | SIFT | Polyphen‐2 | CADD Score | Frequency in gnomAD | Acronym of SAID | AID Mode of Inheritance | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PRF1 | NM_005041.4:c.272C > T (p.Ala91Val) | 10:72 360 387 | Missense | rs35947132 | 3 | Damaging | Probably Damaging | 26 | 0.0292 | FHL | Autosomal recessive | |
| PRF1 | NM_005041.4:c.1153C > T (p.Arg385Trp) | 10:72 358 324 | Missense | rs72358324 | 3 | Damaging | Probably Damaging | 20.8 | 0.0002 | FHL | ||
| STXBP2 | NM_006949.3:c.1034C > T (p.Thr345Met) | 19:7 708 058 | Missense | rs117761837 | 3 | Damaging | Probably Damaging | 26.3 | 0.0106 | FHL | ||
| RAB27A | NM_004580.4:c.17A > G (p.Tyr6Cys) | 15:55 527 116 | Missense | rs145253993 | 1 | Damaging | Probably Damaging | 27 | 0.0001 | FHL | ||
| UNC13D | NM_199242.2:c.670C > T (p.His224Tyr) | 17:73 836 856 | Missense | rs145607492 | 1 | Damaging | Probably Damaging | 25.5 | 0.0002 | FHL | ||
| UNC13D | NM_199242.2:c.610A > G (p.Met204Val) | 17:73 837 042 | Missense | rs144722609 | 1 | Tolerated | Benign | 22.6 | 0.0007 | FHL | ||
| TNFAIP3 | NM_001270508.1:c.406C > T (p.Arg136Cys) | 6:138 196 092 | Missense | rs200740561 | 1 | Damaging | Probably Damaging | 35 | 0.0001 | AISBL | Autosomal dominant | |
| PSTPIP1 | NM_003978.4:c.203C > A (p.Thr68Lys) | 15:77 310 863 | Missense | NA | 1 | Damaging | Possibly Damaging | 25.7 | NA | PAPA | Autosomal dominant | |
| PSTPIP1 | NC_000015.9(NM_003978.4):c.37‐10081C > G | 15:77 300 408 | Splice site a | rs1020233393 | 1 | NA | NA | <10 | NA | PAPA | ||
| NOD2 | NM_022162.2:c.2230C > T (p.Arg744Trp) | 16:50 746 052 | Missense | rs140876663 | 1 | Damaging | Probably Damaging | 26.8 | 0.0001 | Blau syndrome | Autosomal dominant | |
| NOD2 | NM_022162.2:c.2127G > A (p.Trp709*) | 16:50 745 949 | Stop gain | rs776701942 | 1 | NA | NA | 35 | 0.000008 | Blau syndrome | ||
| NOD2 | NM_022162.2:c.679_694del (p.Arg227fs*145) | 16:50 744 498 | Frameshift | NA | 1 | NA | NA | NA | Blau syndrome | |||
| NOD2 | NC_000016.9(NM_022162.2):c.2883‐2A > G | 16:50 759 398 | Splice Site | rs564226539 | 1 | NA | NA | 24.8 | 0.00002 | Blau syndrome | ||
| TNFRSF11A | NM_003839.3:c.1234G > T (p.Asp412Tyr) | 18:60 036 384 | Missense | NA | 1 | Damaging | Probably Damaging | 24.5 | NA | TRAPS11 | Autosomal dominant | |
| TNFRSF11A | NM_003839.3:c.1348C > T (p.Arg450Trp) | 18:60 036 498 | Missense | rs34945627 | 1 | Damaging | Probably Damaging | 22.9 | 0.0009 | TRAPS11 | ||
| NLRP3 | NM_001079821.2:c.2861C > T (p.Thr954Met) | 1:247 607 973 | Missense | rs139814109 | 1 | Damaging | Probably Damaging | 33 | 0.0012 | CAPS | Autosomal dominant. | |
| IFIH1 | NM_022168.3:c.1126G > A (p.Glu376Lys) | 2:163 139 056 | Missense | 1 | Damaging | Probably Damaging | 33 | NA | AGS7 | Autosomal recessive | ||
| IFIH1 | NM_022168.3:c.2597C > T (p.Pro866Leu) | 2:163 128 755 | Missense | rs200833729 | 1 | Tolerated | Possibly Damaging | 23.0 | 0.0004 | AGS7 | ||
| PLCG2 | NM_002661.4:c.82A > T (p.Met28Leu) | 16:81 819 676 | Missense | rs61749044 | 1 | Tolerated | Possibly Damaging | 24.0 | 0.0106 | APLAID | Autosomal dominant | |
| SH3BP2 | NM_001145856.1:c.1600C > T (p.Arg534Trp) | 4:2 834 080 | Missense | rs14876133 | 2 | Damaging | Probably Damaging | 32 | 0.0043 | Cherubism | Autosomal dominant | |
| CARD14 | NM_024110.4:c.1789C > T (p.Arg597Trp) | 17:78 172 328 | Missense | NA | 1 | Damaging | Probably Damaging | 34 | 0.0037 | PSORS2 | Autosomal dominant | |
| CARD14 | NM_024110.4:c.239G > A (p.Arg80Gln) | 17:78 156 479 | Missense | NA | 1 | Tolerated | Probably Damaging | 25 | NA | PSORS2 | ||
| AP1S3 | NM_001039569.1:c.11T > G (p.Phe4Cys) | 2:224 642 579 | Missense | rs116107386 | 1 | Damaging | Probably Damaging | 27.2 | 0.0079 | PSOR15 | Autosomal dominant | |
Abbreviations: AGS7, Aicardi‐Goutieres syndrome 7; AIBSL, autoinflammatory syndrome, familial, Behcet‐like; APLAID, auto‐inflammation and PLCG2‐associated antibody deficiency and immune dysregulation; CAPS, cryopyrin‐associated periodic syndromes; Chr, chromosome; FHL, familial haemophagocytic lymphohistiocytosis; gnomAD, Genome Aggregation Database version 2.1; NA, not available; PAPA, pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome; PSOR15, pustular psoriasis; PSOR2, familial psoriasis; TRAPS11, TNFRSF11A‐associated hereditary fever disease.
All the listed variants were present in heterozygous state in FMF cases and were absent in controls; software version: SIFT version 5.1.1, PolyPhen‐2 version 2.2.2r398, CADD version 1.3.
Results in splice site Loss.