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. 2021 Oct 7;183(3):337–349. doi: 10.1159/000519199

Table 2.

Definite and predicted pathogenic genetic variants identified through tNGS in a cohort of (N = 294) PID patients

Pat.ID Gene Diagnosis Transcript ID Transcript variant Protein variant dbSNP-ID gnomAD frequency CADD score PolyPhen2_Pred SIFT_Pred Varianta Ref. Geneb Ref.
Biallelic variants
 P.204 IGLL1 Agamma-globulinaemia NM_020070.4 c.[258_258del]; [258_258del] p.([Gln88Asnfs*7]; [Gln88Asnfs*7]) RS532338576 0.0009198 22 NA NA 24
 P.71 LRBA CVID LRG_1324 c.[767_767+9del]; [767_767+9del] LRG_1324p1:p.? NA NA NA 25
 P.219 CARMIL2 CID NC_000016.10 c.[467-1G>A]; [467-1G>A] p.? 26 NA NA 26 27
 P.285 CARMIL2 CID NC_000016.10 c.[467-1G>A]; [467-1G>A] p.? 26 NA NA 26
 P.289 CARMIL2 CID NC_000016.10 c.[467-1G>A]; [467-1G>A] p.? 26 NA NA 26
P208 PIK3CD CVID NM_005026.5 c.[1654_1654delG]; [1654_1654delG] p.([Val552Serfs*26]); ([Val552Serfs*26]) 24 NA NA 28 29
 P.273 DCLRE1C (ARTEMIS) Atypical SCID (CID) LRG_54t1 c.[464+1G>A]; [464+1G>A] p.? 30
 P.280 DCLRE1C (ARTEMIS) Atypical SCID (CID) LRG_54t1 c.[464+1G>A]; [464+1G>A] p.?
Monoallelic variants identified
 P.114 NFKB1 CVID NM_003998.4 c.[1012_1012delT]; [1012=] p.[(Ser338Leufs*94)]; [(Ser338=]) 35 NA NA 19, 32 31
 P.183 NFKB1 CVID NM_003998.4 c.[1012_1012delT]; [1012=] p.([Ser338Leufs*94]); ([Ser338=]) 19, 32
 P.122 NFKB1 CVID NM_003998.4 c.[904dupT]; [904=] p.([p.Ser302Phefs*7]); RS773694113 0.000008287 34 NA NA 19, 32
([Ser302])
 P.150 NFKB1 CVID NM_003998.4 c.[1726dupA]; [1726] p.([lle576Asnfs*6]); ([Ile576=]) 35 NA NA 19, 32
 P.200 NFKB1 CID NM_003998.4 c.[875_875delG]; [875=] p.([Gly292Valfs*140]); ([Gly292=]) 19, 32
 P.210 NFKB1 CVID NM_003998.4 c.[470G>C]; [470=] p.([Arg157Pro]); ([Arg157=]) 33 Probably damaging D 19, 32
 P.232 NFKB1 CVID NM_003998.4 c.[691C>T]; [691=] p.([p.Arg231Cys]); ([Arg231=]) 0.00004949 24 Possibly damaging T
 P.233 NFKB1 CVID NM_003998.4 c.[691C>T]; [691=] p.([Arg231Cys]); ([Arg231=]) 0.00004949
 P.254 NFKB1 Unclassified antibody deficiency LRG_1316t1 c.[731-3C>G]; [731=] LRG_1316p1:p.(=) 17 NA NA
 P.26 NFKB2 CVID NM_001077494.3 c.[1097G>A]; [1097=] p.([Gly366Asp]); ([Gly366=]) 0.00002845 19 Probably damaging T 8, 33
 P.181 NFKB2 CVID NM_001077494.3 c.[2557C>T]; [2557=] p.([Arg853*]); ([Arg853]) RS397514332 0.000005329 38 NA T 33
 P.236 NFKBIA CID NM_020529.3 c.[106T>G]; [106=] p.([Ser36Ala)]; ([Ser36=]) 25 Probably damaging T 34 35
 P.154 STAT3 CVID NM_003150.4 c.[653T>C]; [653=] p.([Val218Ala]); ([Val218=]) 27 Benign τ 36 37
 P.278 STAT3 CID NM_003150.4 c.[1276T>C]; [1276=] p.([Cys426Arg]); ([Cys426=]) 22 Benign T 38
 P.282 STAT3 CVID NM_003150.4 c.[859T>G]; [859=] p.([Leu287Val]); ([Leu287=]) 20 Probably damaging D 39
 P.265 STAT3 CID NM_003150.4 c.[0.2144C>T]; [2144=] p.([Thr715Met]); ([Thr715=]) 21 Possibly damaging T 39–40
 P.227 STAT3 Unclassified antibody deficiency NM_003150.4 c.[0.2144C>T]; [2144=] p.([Thr715Met]); ([Thr715=]) 21 Possibly damaging T 40
 P.246 STAT3 HIES NM_003150.4 c.[0.1907C>T]; [1907=] p.([Ser636Phe]); ([Ser636=]) 24 NA ΝΑ 12
 P.56 CTLA4 CVID NM_005214.5 c.[2T>C]; [2=] p.([?]; [Met1]) 24 Possibly damaging D 41 41
 P.165 CTLA4 CID NM_005214.5 c.[118G>A]; [118=] p.([Val40Met]); ([Val40=]) 25 Probably damaging D
 P.215 CTLA4 CVID NM_005214.5 c.[118G>A]; [118=] p.([Val40Met]); ([Val40=]) 25 Probably damaging D
 P.263 IRF2BP2 CVID NM_001077397.1 c.[1597T>G]; [1597=] p.([Cys533Gly]); ([Cys533=]) 24 Probably damaging D 8, 42
 P.159 IRF2BP2 CVID NM_001077397.1 c.[1597T>G]; [1597=] p.([Cys533Gly]); ([Cys533=]) 24 Probably damaging D
 P.257 RELA CVID NM_001145138.2 c.[622G>A]; [622=] p.([Glu208Lys]); ([Glu208=]) 34 Probably damaging D 43
 P.257 GATA2 CVID NM_001145662.1 c.[1343C>A]; [1343=] p.([Ser448Tyr]); ([Ser448=]) 25 Possibly damaging D 44
 P.101 STATI CID NM_007315.4 c.[1198C>G]; [1198=] p.([Leu400Val]); ([Leu400=]) 27 Probably damaging D 45, 14
 P.262 STATI CID NM_007315.4 c.[800C>T]; [800=] p.([Ala267Val]); ([Ala267=]) 22 NA NA 45
 P.164 TCF3 CVID NM_001136139.4 c.[1604T>C]; [1604=] p.([Leu535Pro]); ([Leu535=]) RS373228083 0.000008077 14,5 Probably damaging D 46
 P.166 TCF3 CVID NM_001136139.4 c.[1660C>T]; [1660=] p.([Arg554Trp]); ([Arg554=]) 17 Probably damaging D
 P.270 MYH9 CVID NM_002473.6 c.[3838G>A]; [3838=] p.([Val1280Met]); ([Val 1280=]) RS141582478 0.00006759 23 Possibly damaging D 47–48
 P.253 VAV1 CVID NM_001258206.2 c.[29G>T]; [29=] p.([Trp10Leu]); ([Typ10=]) 29 Probably damaging D 8
 P.253 VAV2 CVID NM_003371.4 c.[2327C>A]; [2327=] p.([Pro776His]); ([Pro776=]) 27 Probably damaging D
 P.294 GATA2 Unclassified antibody deficiency NM_001145662.1 c.[481C>G]; [481=] p.([Pro161Ala]); ([Pro161]) RS34799090 0.008156 26 Probably damaging D
 P.267 SEC61A2 CID NM_001142628.1 c.[718C>T]; [718=] p.([Arg240Cys]); ([Arg240=]) 0.000008239 29 Probably damaging D
 P.63 PIK3R1 CVID NC_000005.9 c.[635-11T>A]; [635=] p.(=) 0.000008434 16 NA NA 49
 P.63 GATA2 CVID NM_001145662.1 c.[30G>C]; [30=] p.([Trp10Cys]); ([Trp10=]) 27 Possibly damaging D
 P.127 PIK3R4 Unclassified antibody deficiency NM_014602.3 c.[1039C>T]; [1039=] p.([Arg347Trp]); ([Arg347]) 0.0013 32 Possibly damaging T
 P.124 SOCS1 CVID NM_003745.2 c.[147_153del]; [147=] p.([Pro50Thrfs*33]); ([Pro50 =]) 0.0001096 14 NA NA 50
 P.135 PIK3R1 CVID NM_181504.4 c.[18G>T]; [18=] p.([Trp6Cys]); ([Trp6=]) 0.00023 16 Probably damaging D 49
 P.182 PIK3R4 CVID NM_014602.3 c.[1039C>T]; [1039=] p.([Arg347Trp]); ([Arg347]) 0.001376 32 Possibly damaging T
 P.264 REL Unclassified antibody deficiency NM_001291746.2 c.[395T>C]; [395=] p.([Val132Ala]); ([Val132=]) 24 Probably damaging NA 43
 P.266 PIK3R4 CVID NM_014602.3 c.[3341A>G]; [3341=] p.([Tyr1114Cys]); ([Tyr1114=]) RS372167716 0.000048 28 Probably damaging T
X-linked variants
 P.279 BTK Agammaglobulinaemia NM_000061.3 c.[427C>T]; [0] p.His 143Tyr 26 Probably damaging NA 51
Compound heterozygous variants
 P.64 RAG1 CID NM_000448.3 c.[1431del; 1123C>G]; [1420C>T] p.([Phe478Serfs*14; His375Asp]); ([Arg474Cys]) NA, 25,29 Probably damaging NA, D 52–53 54
Uncertain allele phase
 P.108 USP8 CVID NM_001128610.3 c.1888A>T (;)1888_1890del p.(Lys630*)(;) (Lys630del) 41 NA T 55
 P.182 RELB CVID NM_006509.4 c.1291G>C (;) 1579G>A p.(Glu431Gln)(;) (Glu527Lys) 31, 17 Possibly damaging T 56

CADD, combined annotation-dependent depletion; CID, combined immunodeficiency; CVID, common variable immunodeficiency; D, deleterious; F, female; freq., frequency; gnomAD, genome aggregation database; M, male; MSC, mutation significance cut-off; NA, not available; Pat. ID, patient identification number; pred., prediction; ref., reference; ref. seq., reference sequence; SCID, severe combined immunodeficiency; T, tolerated; tNGS, targeted next-generation sequencing.

a

Previous report on the pathogenicity of the identified variant.

b

Previous report on the involvement of the mutated gene in primary immunodeficiency.