Table 1.
GATA2 germline variants reported in families or individuals displaying one or more GATA2 deficiency syndrome (G2DS) phenotypes
| Number individuals | Familial (F)/de novo (D) | GATA2 protein (NP_116027.2) | GATA2 cDNA (NM_032638.5) | Mutation effect | ACMG/AMP classification (curated) | ACMG/AMP criteria | Overall Phenotype | Chromosomal Abnormalities |
|---|---|---|---|---|---|---|---|---|
| 1 | N/A | p.(Glu6Alafs*178) | c.17_18del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | F | p.(Gln20*) | c.58C>T | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | T‐ALL, HA, ID | 45,XX,dic(21;22)(p11.2;p11.2) |
| 7 | F |
p.(Gly28Alafs*52) (in cis p.(His26Pro)) |
c.77A>C/c.83delG | FS | Pathogenic | PVS1, PS4, PM2, PP1_Moderate | M/A, ID, L, HA | −7 |
| 3 | F | p.(Glu44*) | c.130G>T | NS | Pathogenic | PVS1, PS4_Moderate, PM2 | L, HA, ID | |
| 1 | N/A | p.(Ser54*) | c.161C>A | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | F |
p.(Tyr59*) (in cis p.?) |
c.177C>G (in cis c.[140T>G;142T>C;145T>C]) |
NS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | +8 |
| 1 | D | p.(Arg69Leufs*115) | c.206_208delGCGinsT | FS | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | M/A | |
| 1 | N/A | p.(Val70Leufs*114) | c.207_208delCG | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | der(1;7) add |
| 1 | D | p.? | c.222_229+6del14ins21 | INDEL | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | M/A | +8 |
| 2 | F | p.? | c.229+13_229+14insGCCins203_229+13 | INDEL | Likely Pathogenic | PS4_Moderate, PM2, PP3 | M/A, ID | +8 |
| 3 | F | p.(Arg78Profs*107) | c.232dup [c.230‐1_230insC] | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, L, HA | −7 |
| 1 | N/A | p.(Gly82Argfs*103)[G81fs*] | c.243delinsGC | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | NK |
| 1 | N/A | p.(Arg86Profs*98) [C85fs*] | c.257_258del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | −7 |
| 1 | N/A | p.(Arg86Alafs*33) | c.256del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, M/A, HA | |
| 1 | N/A | p.(Gly101Alafs*18) [G101Afs*16] | c.302del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, CMML, ID, HA | del(11)(q13q23), −7, +8 |
| 3 | N/A | p.(Ala103Glnfs*16) | c.303del | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A |
−7, der(1;7)(q10;p10), der(1;7) add |
| 1 | N/A | p.(Ala103Glnfs*16) | c.306del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7, add |
| 5 | F | p.(Leu105Profs*15) | c.312_313dup | FS | Pathogenic | PVS1, PS4, PM2 | M/A, ID, L, HA | ‐7 |
| 1 | N/A | p.(Ser106Cysfs*78) | c.317_318del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID | NK |
| 2 | F | p.(Ala107Cysfs*78) [S106fs] | c.318dup [c.318_319insT] | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | ID, L | |
| 15 | F | p.(Thr117=) | c.351C>G | SPL | Pathogenic | PS3_Very Strong, PS4, PM2, PP1_Strong, PP3 | M/A, ID, L, HA, NS |
−7, +8, Chr1 translocation |
| 1 | N/A | p.(Val118Glyfs*100) [V618fs] | c.353del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Gly136Argfs*49) | c.404dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | |
| 1 | N/A | p.(Ser139Cysfs*78) | c.414_417del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, M/A, HA, L | |
| 1 | N/A | p.(Ser139Cysfs*45) | c.416_417del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Val140Cysfs*45) [V140Cfs*44] | c.417dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | NK |
| 2 | F | p.(Tyr141*) | c.423C>A | NS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID | −7 |
| 1 | F | p.(Gly146Valfs*72) | c.437del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | NK |
| 1 | N/A | p.(Glu180*) | c.538G>T | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | NK |
| 1 | N/A | p.(Thr188Hisfs*14) | c.561dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | NK |
| 1 | D | p.(Ala194Serfs*8) | c.579dup | FS | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | L, M/A | −7 |
| 1 | N/A | p.(Ala198Glyfs*20) | c.593del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | HA, ID | |
| 1 | F | p.(Gly199Leufs*22) | c.586_593dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | −9q |
| 5 | F | p.(Gly200Valfs*18) [G199fs*] |
c.599del [c.594delG] |
FS | Pathogenic | PVS1, PS4, PM2 | M/A, ID, L | −7 |
| 11 | F/D | p.(Ser201*) [G200fs] | c.599dup [c.599_600insG] | NS | Pathogenic | PVS1, PS4, PM2 | M/A, ID, HA, L | +8, −7 |
| 1 | N/A | p.(Arg204*) | c.610C>T | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | 46,XX,der(9)t(1;9)(q12;q12), r(9)(q12q?34)[15]/46,XX [9] |
| 1 | N/A | p.(Val211Argfs*72) | c.627_630dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Glu224*) | c.670G>T | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | NK |
| 1 | N/A | p.(Leu229Cysfs*5) | c.685del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Gly237Alafs*89) [M236Ifs325*] | c.710del [c.708delC] | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | HA, L, ID | |
| 2 | N/A | p.(Ile246Hisfs*36) [P245fs*] | c.735dup [c.735_736insC] | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | ID, M/A, HA | |
| 1 | F | p.(Tyr260Cysfs*25) [Y260fs*24, D259fs*] | c.769_778dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | −7 |
| 1 | N/A | p.(Phe265Glufs*58) | c.793_802del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | |
| 3 | F | p.(Gly268*) | c.802G>T | NS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID, L |
−13q ‐7 +8 |
| 2 | N/A | p.(Gly273Thrfs*8) | c.817_818del [c.814_815del] | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A |
‐7 +8 |
| 1 | N/A | p.(Pro274Thrfs*8) [G273fs*] | c.818dupG [c.819insG] | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | Other |
| 1 | F | p.(Ala286Val) | c.857C>T | MS | Likely pathogenic | PS3, PS4_Supporting, PM2, PP3 | CMML | |
| 1 | N/A | p.(Ser290*) | c.869C>A | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | HA/ID | |
| 3 | F | p.(Cys298Leufs*86) | c.892dup | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | ID, M/A |
Chr1‐7 translocation +8 |
| 2 | F | p.(Trp306Alafs*77) | c.915_916del | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID, HA | −7 |
| 1 | N/A | p.(Trp306*) | c.917G>A | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA, L, ID | −7 |
| 1 | N/A | p.(Thr311Argfs*71) | c.932_937delinsG | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | F | p.(His313Tyr) | c.937C>T | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PP3 | M/A, ID | −5, −7, +8, add10, −12, −18, −21 |
| 1 | F | p.(Tyr314Cysfs*66) | c.941_951del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | −7 |
| 1 | N/A | p.(Leu315Pro) | c.944T>C | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PP3 | ID | |
| 1 | N/A | p.(Ala318Thrfs*12) | c.941_951dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | −6 |
| 1 | F | p.(Ala318Thr) | c.952G>A | MS | Pathogenic | PS3, PS4_Supporting, PM1, PM2, PP3 | M/A, ID, HA | +1,der(1:7)(q10:p10), +8 |
| 1 | F | p.(Cys319Serfs*5) | c.956_962del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, HA | |
| 1 | N/A | p.(His323Glnfs*61) | c.968dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Gln328*) | c.982C>T | MS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | dic(1;15)(?;?) |
| 13 | F/D | p.(Arg330*) | c.988C>T | NS | Pathogenic | PVS1, PS4, PM2 | M/A, ID, L, HA, JMML |
−7, +8, +1 |
| 1 | N/A | p.(Leu332Thrfs*53) | c.989_992dup [c.992_993insGACC] | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA, L | −7, +8 |
| 1 | N/A | p.(Leu332Glnfs*60) | c.970_994dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 7 | F | p.(Arg337*) | c.1009C>T | NS | Pathogenic | PVS1, PS4, PM2 | M/A, ID, L, HA | −7 |
| 1 | N/A | p.? | c.1017+1del | SPL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 2 | N/A | p.? [S340Gfs*99] | c.1017+2T>G | SPL | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID, HA | −7 |
| 1 | D | p.? [S340Afs*49] | c.1017+2T>C | SPL | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | M/A, HA, L, ID | |
| 2 | F |
p.? INT enhancer (del ETS site) |
c.1017+513_1017+540del (c.1017+512del28) | REG | Likely Pathogenic | PS3_Supporting, PS4_ Moderate, PM1, PM2 | M/A, ID, HA | |
| 30 | F |
p.? INT enhancer (ETS site) |
c.1017+572C>T | REG | Pathogenic | PS3, PS4, PM1, PM2, PP1_Strong | M/A, ID, L, HA, CMML, ALL, B‐ALL |
−7 +8 +1 der(Y)t(Y;1)(q11.23;q21) der(1;7)(q10;p10) |
| 1 | N/A | p.? | c.1018‐11_1027del | SPL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 2 | N/A | p.? | c.1018‐10_1037del | SPL | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A | −7 |
| 2 | N/A | p.? [A341Rfs*38] | c.1018‐3_1031del | SPL | Pathogenic | PVS1, PS4_ Moderate, PM2 | ID, L, HA, HL | |
| 2 | F | p.? | c.1018‐2A>G | SPL | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, L | −7 |
| 1 | N/A | p.? | c.1018‐2A>T | SPL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 2 | N/A | p.? [S340‐N381del] | c.1018‐1G>A | DEL | Likely Pathogenic | PVS1_Strong, PS4_ Moderate, PM2 | M/A,HA, ID | der(22)t(1;22)(q12;p13)/der(15)t(1;15)(q12;p13) |
| 1 | N/A | p.? [S340‐N381del] | c.1018‐1G>T | DEL | Likely Pathogenic | PVS1_Strong, PS4_Supporting, PM2 | HA,ID | |
| 2 | F | p.(Ser340Lysfs*40) | c.1018_1028del | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID | NK |
| 1 | N/A | p.(Ser340Trpfs*47) | c.1019del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Ala341Aspfs*53) | c.1019_1020insCGACTGGGAGGGCAAGGCAG | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA, L, ID | |
| 1 | N/A | p.(Ala341Profs*46) | c.1021del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | HA, ID, L | |
| 1 | N/A | p.(Ala341Profs*45) | c.1021_1024del [c.1019_1022del] | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | L, M/A, HL | |
| 3 | F | p.(Ala341Serfs*39) | c.1021_1031del | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID | −7, +8 |
| 1 | N/A | p.(Ala342Argfs*42) | c.1023dup | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | NK |
| 2 | F | p.(Ala342Profs*45) | c.1023del | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | ID, L | NK |
| 2 | N/A | p.(Ala342del)l [341delA] | c.1024_1026del [c.1021_1023] | DEL | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A | −7 |
| 1 | N/A | p.(Arg343Profs*42) [A342Gfs*41] | c.1025_1026insGCCG | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, HA | |
| 2 | F | p.(Arg344Glnfs*41) | c.1023_1026dup | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID, HA | −7 |
| 3 | N/A | p.(Arg344Glyfs*43) | c.1020_1029dup | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID, L, HA | NK |
| 1 | D | p.(Arg344Lysfs*37) | c.1031_1049del | FS | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | M/A | NK |
| 1 | N/A | p.(R344Kfs*40) | N/A | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | NK |
| 1 | N/A | p.(Gly346Serfs*40) |
c.1035_1036ins TCTGGCC |
FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, HA | |
| 1 | D | p.(Thr347Argfs*38) | c.1035_1038dup | FS | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Thr347Argfs*42) | c.1023_1038dup (c.1038_1039insCGCCAGAAGAGCCGGC) | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 2 | F | p.(T347fs) | 16bp tandem dup | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | ID, HA | |
| 1 | N/A | p.(Cys348Valfs*39) | c.1041del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, M/A, HA | −7 |
| 1 | D | p.(Cys349Phe) [C348F] | c.1046G>T | MS | Likely Pathogenic | PS2, PS4_Supporting, PM1, PM2, PM5, PP3 | M/A | −7 |
| 1 | D | p.(Cys349Arg) | c.1045T>C | MS | Pathogenic | PS2, PS4_Supporting, PM1, PM2, PM5, PP3 | M/A, ID |
46,XY,der(3)t dic(1;3)(p11; p25) |
| 1 | N/A | p.(Cys349Gly) | c.1045T>G | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP3 | ID, M/A,L | |
| 1 | N/A | p.(Asn351Ser) | c.1052A>G | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PP3 | M/A | −7 |
| 1 | F | p.(Cys352Arg) | c.1054T>C | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP3 | M/A | |
| 1 | N/A | p.(Cys352Gly) | c.1054T>G | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP33 | M/A | −7 |
| 1 | N/A | p.(Cys352Valfs*35) | c.1054del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, M/A, HA, L | NK |
| 1 | N/A | p.(Cys352Phe) | c.1055G>T | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP3 | M/A | der(1;7)(q10;p10),+1 |
| 2 | F/D | p.(Thr354Pro) | c.1060A>C | MS | Pathogenic | PS2, PS4_Moderate, PM1, PM2, PM5, PP3 | M/A, ID, L, HA | NK |
| 53 | F | p.(Thr354Met) | c.1061C>T | MS | Pathogenic | PS3, PS4, PM1, PM2, PM5, PP1_Strong, PP3 | M/A, ID, L, HA |
−7, +8, +21, −5q, 1q abnormality, isochromosome 17, F100 t(1q:7p) +8 replaced by monodicentric 6 |
| 1 | F | p.(Thr354Arg) | c.1061C>G | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP3 | M/A, ID | 46,XX [20]/92,XXXX [2] |
| 2 | F | p.(Thr358del) [355delT] |
c.1065_1067del [c.1063_1065delACA] |
DEL | Pathogenic | PS3, PS4_Moderate, PM2, PM4 | M/A |
−7 +8 |
| 1 | N/A | p.(Thr358del) | c.1072_1074del | DEL | Pathogenic | PS3, PS4_Moderate, PM2, PM4 | ID | |
| 1 | N/A | p.(Thr356_Asn365del) | c.1066_1095del | DEL | Likely Pathogenic | PS4_Supporting, PM2, PM4_Strong | M/A | −7 |
| 2 | N/A | p.(Thr357Ala) | c.1069A>G | MS | Likely Pathogenic | PS4_ Moderate, PM1, PM2, PM5, PP3 | M/A |
der(1;7), add +8 |
| 1 | N/A | p.(Thr357Ile) | c.1070C>T | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP3 | M/A, ID | NK |
| 1 | F |
p.(Thr358Asn), p.(Leu359Val) (in‐cis) |
c.1073C>A c.1075T>G |
MS | Pathogenic/VUS | PS3, PS4_Supporting, PM1, PM2, PP3/PM1, PM2, PM5, PP3, BP2 | M/A, HA, ID | |
| 1 | F | p.(Leu359Val) | c.1076T>C | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PP3 | M/A, ID, L |
46,XX,del(5)(q2?3q 3?3) [18]/46,XX |
| 3 | F | p.(Trp360Arg) | c.1078T>A | MS | Likely Pathogenic | PS4_Moderate, PM1, PM2, PM5, PP3 | ID, L, HA | |
| 1 | F | p.(Trp360Leu) | c.1079G>T | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP3 | M/A, HA, ID | −7 |
| 2 | F | p.(Arg361Gly) | c.1081C>G | MS | Likely Pathogenic | PS4_Moderate, PM1, PM2, PM5, PP3 | M/A, ID, L | |
| 7 | F | p.(Arg361Cys) | c.1081C>T | MS | Likely Pathogenic | PS4, PM1, PM5, PP3 | MA, ID, L, HA | −7 |
| 1 | D | p.(Arg361Leu) | c.1082G>T | MS | Pathogenic | PS2, PS3, PS4_Supporting, PM1, PM2, PM5, PP3 | L, HA, ID | |
| 8 | F | p.(Arg361His) | c.1082 G>A | MS | Pathogenic | PS4, PM1, PM2, PM5, PP3 | M/A, NS, ID | −7, +8 |
| 1 | N/A |
p.(Arg362_Asn365 del) [R361del4] |
c.1084_1095del [c.1083_1094del12] |
DEL | Likely Pathogenic | PS4_Supporting, PM2, PM4_Strong | M/A, ID, HA | −7, +21, +8 |
| 17 | F/D | p.(Arg362*) | c.1084C>T | NS | Pathogenic | PVS1, PS4, PM2 | M/A, ID, L, HA |
−7, add +8 −20q |
| 2 | F | p.(Arg362Pro) | c.1085G>C | MS | Likely Pathogenic | PS4_ Moderate, PM1, PM2, PP3 | M/A, ID, L |
−7 +8 |
| 1 | N/A | p.(Asp367Thrfs*20) | c.1099del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA, ID | |
| 3 | F | p.(Asp367Glyfs*17) | c.1099dup [c.1099insG] | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID, HA | NK |
| 1 | N/A | p.(Pro368Argfs*15) | c.1103_1104del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | NS | |
| 1 | N/A | p.(Cys370Trp) | c.1110C>G | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PP3 | M/A | −7 |
| 4 | N/A | p.(Asn371Lys) | c.1113C>A | MS | Pathogenic | PS1, PS4, PM1, PM2, PP3 | MA, L, ID |
−7 +8 |
| 2 | N/A | p.(Asn371Lys) | c.1113C>G | MS | Pathogenic | PS1, PS4_Moderate, PM1, PM2, PP3 | M/A, HA,ID | −7, +mar |
| 1 | N/A | p.(Asn371Lysfs*16) | c.1113del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7, +8 |
| 6 | F | p.(Ala372Thr) | c.1114G>A | MS | Likely Pathogenic | PS4, PM1, PM2, PP3 | M/A, ID, L | −7, +15, +20 t(11;19), +8 |
| 3 | F |
p.(Cys373_Tyr377del) [C373del5] |
c.1117_1131del [c.1116_1130del15] | DEL | Likely Pathogenic | PS4_ Moderate, PM2, PM4_Strong* | M/A, ID | −7 |
| 1 | N/A | p.(Cys373Tyr) | c.1118G>A | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PM5, PP3 | M/A, ID, L |
+1 −15 |
| 1 | N/A | p.(Cys373Arg) | c.1117T>C | MS | Likely Pathogenic | PS3_Supporting, PS4_Supporting, PM1, PM2, PM5, PP3 | L, M/A, ID | −7 |
| 1 | N/A |
p.(Leu375Val), p.? |
c.1123C>G in‐cis with 355 bp of GATA2 locus (part of last intron & exon) that has been duplicated and inserted into the last exon |
MS, INS |
Likely Pathogenic | PM1, PM2, PM5, PP3 | M/A | NK |
| 3 | F | p.(Leu375Phe) | c.1123C>T | MS | Likely Pathogenic | PS4_Moderate, PM1, PM2, PM5, PP3 | M/A, ID, L, HA | −7, +8, +20 |
| 2 | D | p.(Leu375Profs*12) | c.1124del | FS | Pathogenic | PVS1, PS2, PS4_ Moderate, PM2 | M/A | −7 |
| 1 | D | p.(Tyr376*) | c.1128C>G | NS | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | M/A | NK |
| 1 | N/A | p.(Tyr377Asp) | c.1129T>G | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PP3 | ID, HA | |
| 1 | N/A | p.(Lys378*) | c.1132A>T | NS | Pathogenic | PVS1, PS4_Supporting, PM2 | HA, ID | hyperdiploidy (>80 chr), +8 |
| 2 | F | p.(Lys378Asnfs*12) | c.1126_1133dup | FS | Pathogenic | PVS1, PS4_ Moderate, PM2 | HA, ID, M/A | NK |
| 1 | N/A | p.(Asn381Metfs*6) | c.1142del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | NK |
| 1 | D |
p.? [S340_N381del, V382Gfs*23 or N381_V382ins41] |
c.1143+2T>A | SPL | Pathogenic | PVS1, PS2, PS4_Supporting, PM2 | M/A, ID, HA | +8 |
| 3 | D | p.? [N381fs*20] | c.1143+5G>A | SPL | Likely Pathogenic | PS3, PS4_Moderate, PM2, PM6_Supporting | ID, M/A | |
| 2 | N/A | p.? | c.1143+5G>C | SPL | Likely Pathogenic | PS1_Supporting, PS4_Moderate, PM2, PP3 | M/A, ID | +8 |
| 1 | N/A | p.? [N381fs*] | c.1143+200_1198del | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | HA, ID, L | NK |
| 3 | F | p.(Pro385Gln) | c.1154C>A | MS | Likely Pathogenic | PS4_ Moderate, PM1, PM2, PP3 | M/A, ID, L, T‐ALL | −7 |
| 1 | N/A | p.(Thr387Asn) | c.1160C>A | MS | Likely Pathogenic | PS4_Supporting, PM1, PM2, PP3 | M/A | +8 |
| 2 | F | p.(Met388Val) | c.1162A>G | MS | Likely Pathogenic | PS4_ Moderate, PM1, PM2, PM5, PP3 | M/A, HA, ID |
−7 +8 |
| 5 | F | p.(Met388Thr) | c.1163T>C | MS | Likely Pathogenic | PS4, PM1, PM2, PM5, PP3 | ID, HA | |
| 1 | N/A | p.(Lys390Glu) | c.1168A>G | MS | Likely Pathogenic | PS4_Moderate, PM1, PM2, PP3 | M/A | der(1;7) add |
| 1 | N/A | p.(Glu391Glyfs*85) | c.1172_1175del | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, HA | |
| 12 | F | p.(Arg396Trp) | c.1186C>T | MS | Pathogenic | PS4, PM1, PM2, PM5, PP3 | M/A, ID, L, HA | +8, +mar, −7, −21 |
| 24 | F/D | p.(Arg396Gln) | c.1187G>A | MS | Pathogenic | PS2, PS3, PS4, PM1, PM2, PM5, PP1_Moderate, PP3 | M/A, ID, L, HA | +8, −7, +11, der(1;16), add |
| 3 | F | p.(Arg396Leu) | c.1187G>T | MS | Likely Pathogenic | PS3_Supporting, PS4_ Moderate, PM1, PM2, PM5, PP1_Supporting, PP3 | M/A, HA, ID | |
| 22 | F | p.(Arg398Trp) | c.1192C>T | MS | Pathogenic | PS3, PS4, PM1, PM2, PM5, PP1_Moderate, PP3 | M/A, ID, HA, CMML, JMML, L | +1, −7, +8, ‐X |
| 4 | F | p.(Arg398Gln) | c.1193G>A | MS | Likely Pathogenic | PS4, PM1, PM5, PP3 | M/A, ID | −7, +8 |
| 1 | N/A | p.(Lys406Serfs*77) |
c.1200_1216dup [c.1216_1217ins17] |
FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 |
| 1 | N/A | p.(Phe428Leufs*108) | c.1281dup [c.1281_1282insC] | FS | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | |
| 1 | N/A | p.(His442Glnfs*95) | c.1322_1325dup | FS | Likely pathogenic | PVS1_Moderate, PS4_Supporting, PM2 | M/A | |
| 8 | F | p.(Ser447Arg) | c.1339A>C | MS | Pathogenic | PS1, PS4, PM2, PP1_Moderate, PP3 | M/A, ID, HA | +8 |
| 2 | N/A | p.(Ser447Arg) | c.1341C>A | MS | Likely pathogenic | PS1, PS4_Moderate, PM2 | M/A | −7 |
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | L, M/A, ID, DF, NS | +21 | |
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, DF, NS, HA | ||
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | HA, ID | ||
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, HA | ||
| 2 | N/A |
Deletion (whole protein) |
c.1‐?_1443+?del | DEL | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID | NK |
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, DF, NS, HA | −7 | |
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA, ID, L | −7, +8 | |
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA, ID | ||
| 1 | N/A |
Deletion (whole protein) |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 | |
| 1 | N/A | del3q21 | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID, NS | del3q21, −7 | |
| 1 | N/A | Deletion | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA, ID | 45,XY,‐7[7]/46,XY,‐7,+mar[10]/46,XY[8] | |
| 1 | N/A | Deletion | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | HA, ID | ||
| 1 | F |
Delete ATG start codon |
DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | t(2;12)(p21;p13) | |
| 3 | F | p.? (M1del290) | c.‐45‐155_871+527del | DEL | Pathogenic | PVS1, PS4_ Moderate, PM2 | M/A, ID, L, HA | NK |
| 1 | N/A | p.? | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, HA | ||
| 1 | F | p.? | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A | −7 | |
| 1 | F | p.? | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | (7q22)x1,(7q31)x1 [260/400] | |
| 1 | F | del ZF2 & C‐terminus | c.1018‐? | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | M/A, ID | |
| 1 | N/A | del ZF2 & C‐terminus | c.1018‐?_1443+?del | DEL | Pathogenic | PVS1, PS4_Supporting, PM2 | ID, M/A |
Note: This table summarizes germline GATA2 likely pathogenic/pathogenic variants with full details available in Table S1. All mutations are numbered from the ATG start codon of GATA2 NM_032638.5 and NP_116027.2. Where the original published nomenclature differs, the original published mutation is indicated in square brackets []. For each mutation, the observed phenotypes for each individual were combined to generate the overall phenotype. Overall phenotypes: CMML, chronic myelomonocytic leukemia; DF, dysmorphic features; HA, hematological abnormality; HL, hearing loss; ID, immunodeficiency; JMML, juvenile myelomonocytic leukemia; L, lymphedema; M/A, MDS and/or AML; NS, neurologic symptoms; T‐ALL, T‐cell acute lymphoblastic leukemia. Mutation effect: DEL, large deletion; FS, frameshift; INDEL, small insertion/deletion; MS, missense; NS, nonsense; REG, regulatory; SPL, splice site.