Table 6.
Molecular structures identified in samples with reproducible discrepancy between prediction and serology
| Samples (n) | Phenotype |
Donor |
ExAC frequency* |
||||||
|---|---|---|---|---|---|---|---|---|---|
| predicted | found | polymorphisms | protein | antigens | snp number | non-Finnish Europeans | deduced genotype | evidence for causality / association | |
| Glycophorin B | |||||||||
| False-negative antigen prediction | |||||||||
| 3 | S−s+ | S+s+ | c.143C/T; c.161G/A | 48 Met / Thr | S / s | rs7683365 | 0.3802; | GYPB*04/GYPB*24 | disrupted primer |
| 54 Arg / His | Mit+ | rs370332485 | 0.0002869 | binding | |||||
| 1 | S−s+ | S+s+ | c.143C/T; c.161G/C | 48 Met / Thr | S / s | rs7683365 | 0.3802; | GYPB*04/GYPB*03. | disrupted primer |
| 54 Arg / Pro | unknown | absent | (c.161C)† | binding | |||||
| 1 | S+s− | S+s+ | c.143C/T; c.163T/C; | 48 Met / Thr; | S / s | rs7683365 | 0.3802; | GYPB*04/GYPB*03. | disrupted primer |
| c.251 G/C | 55 Phe / Leu | unknown | rs755129621 | 0.00008228 | (c.163C,251C) or | binding | |||
| 84 Ser/ Thr | unknown | rs1132783 | 0.232 | GYPB*04(c.251C)/ | |||||
| GYPB*03(c.163C) | |||||||||
| Lutheran | |||||||||
| Lub− (including Lub mod) | |||||||||
| 2 | Lu(a+b+) | Lu(a+b−) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19.(c.586A)/ | no cause identified§: |
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | Lu*02 | ||||
| c.1615 A/G | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | |||||
| 1 | Lu(a+b+) | Lu(a+b−) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.(c.586A)/ | no cause identified§: |
| Elution pos | c.586 G/A | 196 Val / Ile | unknown | rs28399654 | 0.03308; | Lu*02 | |||
| 1: | Lu(a+b+) | Lu(a+b−) | c.-4036_-4029del (het) | Non-coding; | unknown; | - | NC; | LU*01.19.(c.586A)/ | the deletion is 63 bp 5′ |
| c.230 G/A; | 77 Arg / His; | Lub+/Lua+; | rs28399653 | 0.0382; | Lu*02(-4036_ | of the BCAM promoter | |||
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | -4029del)† | ||||
| c.1615 A/G | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | |||||
| 1 | Lu(a+b+) | Lu(a+b−) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19.(c.586A)/ | p < 0.01 |
| elution neg | c.529 G/C; | 177 Gly / Arg | unknown; | rs777617369 | W: 0.0001225 | Lu*02.(c.529C)† | |||
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | |||||
| c.1615 A/G | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | |||||
| 1 | Lu(a+b+) | Lu(a+b−) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01 / LU*02.c | p < 0.05 |
| c.711 C/T | (silent) | -; | rs3810140 | 0.06594; | (711T, 714T, 733A)† | ||||
| c.714 C/T | (silent) | -; | rs3810140 | 0.06590 | |||||
| c.733 G/A | 245 Glu / Lys | unknown | rs762681823 | 0.000015603 | |||||
| 2 | Lu(a+b+) | Lu(a+b−) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.(c.586A)/ | p < 0.01 |
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | Lu*02.-13.(c.997A)† | ||||
| c.997 G/A; | 333 Gly / Arg; | unknown; | rs147593462 | W:0.00002477 | |||||
| c.1671 C/T | (silent) | -; | rs28399658 | 0.04170; | |||||
| c.1742 A/T | 581 Gln / Leu | Lu:13 / −13 | rs28399659 | 0.04632 | |||||
| 1 | Lu(a+b+) | Lu(a+b−) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19/Lu*02. | unsure: p < 0.05 |
| c.1612 G/A; | 538 Gly / Ser; | unknown; | rs145626518 | 0.0005108; | (c.1612A)† or | ||||
| c.1615 A/G | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | LU*01/ LU*02.10. | ||||
| (c.1612A)† | |||||||||
| 1 | Lu(a+b+) | Lu(a+b−) | c.100_105del‡; | 34_35delArgLeu‡ | LU:12/LU:-12; | - | 0.001679; | LU*01.19.(c.586A)/ | unsure: p < 0.05 |
| elution pos | c.230 G/A; | 77 Arg / His; | Lub+/Lua+; | rs28399653 | 0.0382; | Lu*02.-12.1 | |||
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | |||||
| c.1615 A/G | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | |||||
| Lub weak | |||||||||
| 1 | Lu(a+b+) | Lu(a+b+w) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19.(c.586A)/ | no cause identified§: |
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | Lu*02 | ||||
| c.1615 A/G | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | |||||
| 1 | Lu(a+b+) | Lu(a+b+w) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19 / | p < 0.05 |
| c.1183 C/T; | 395 Arg / Cys; | unknown; | rs761656868 | 0.00003004; | Lu*02.(c.1183T) † | ||||
| c.1615 T/A | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | |||||
| 1 | Lu(a+b+) | Lu(a+b+w) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19./(c.529C) / | unsure: p < 0.05 |
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | Lu*02.-26 | ||||
| c.1495 C / T | 499 Arg / Trp | LU:26/-26 | rs148391498 | 0.0007812 | |||||
| 1 | Lu(a+b+) | Lu(a−b+) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19.(c.937T) †/ | p < 0.01 |
| c.586 G/A; | 196 Val / Ile; | unknown; | rs28399654 | 0.03308; | Lu*02 | ||||
| c.937 G/C | 313 Val / Leu | unknown; | rs199762962 | W:0.000008293 | |||||
| c.1615 T/A | 539 Thr / Ala | Aua+/Aub+ | rs1135062 | 0.29932 | |||||
| 1 | Lu(a+b+) | Lu(a−b+) | c.230 G/A; | 77 Arg / His | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.(c.586A). | p < 0.01 |
| c.1722 A/T | 574 Lys / Asn | unknown; | - | absent | (c.1722T) †/ | ||||
| c.1742 A/T | 581 Gln / Leu | Lu:13 / −13 | rs28399659 | 0.04632 | Lu*02.-13 | ||||
| False-negative antigen prediction | |||||||||
| 1 | Lu(a+b−) | Lu(a+b+) | c.230 G/A; | 77 Arg / His; | Lub+/Lua+; | rs28399653 | 0.0382; | LU*01.19 / | disrupted primer |
| c.240 G/A | (silent) | - | rs779970171 | W:0.00002868 | LU*02.(c.240A) | binding | |||
| Kell | |||||||||
| Kpb- (including mod phenotype) | |||||||||
| 1 | Kp(a+b+) | Kp(a+b−) | c.841 C/T; | 281 Arg / Trp; | Kpb+ / Kpa+; | rs8176059 | 0.010544; | KEL*02.03 / | p < 0.01 |
| c.1658 C/T | 553 Pro / Leu | unknown | rs1431256906 | absent | KEL*01.01. | ||||
| (c.1658T) † | |||||||||
| 1 | Kp(a+b+) | Kp(a+b−) | c.841 C/T; | 281 Arg / Trp; | Kpb+ / Kpa+; | rs8176059 | 0.010544; | KEL*02.03 / | known null allele |
| c.1546 C/T | 516 Arg / Stop | K null | rs8176034 | 0.00007494 | KEL*02N.17 | ||||
| Kpa- (including mod phenotype) | |||||||||
| 6 | Kp(a+b+) | Kp(a−b+) | c.257 G/A; | 86 Arg / Gln; | K mod; | rs777011308 | 0.00001501; | KEL*02M.13/ | known mod allele |
| Elution | c.841 C/T | 281 Arg / Trp | Kpb+ / Kpa+ | rs8176059 | 0.010544 | KEL*01.01 | |||
| negative | |||||||||
| 1 | Kp(a+b+) | Kp(a−b+) | c.257 G/A; | 86 Arg / Gln; | K mod; | rs777011308 | 0.00001501; | KEL*02M.13/ | known mod allele |
| c.841 C/T; | 281 Arg / Trp; | Kpb+ / Kpa+ | rs8176059 | 0.010544; | KEL*01.01. | ||||
| c.1680 A/C | (silent) | - | rs8176036 | 0.04956 | (c.1680C) | ||||
| Colton | |||||||||
| Coa-(including mod phenotype) | |||||||||
| 1 | Co(a+b+) | Co(a−b+) | c.-101 C/G; | Non-coding; | -; | NC; | CO*01. | promoter, possibly transcription factor binding inhibited | |
| c.134 C/T | 45 Ala / Val | Coa+ / Cob+; | rs28362692 | 0.03976 | (c.-101G)† / | ||||
| CO*02 | |||||||||
| 1 | Co(a+b+) | Co(a−b+) | c.134 C/T; | 45 Ala / Val; | Coa+ / Cob+; | rs28362692 | 0.03976 | CO*01.(c.494A) / | no cause identified§: |
| c.494 G/A | 165 Gly / Asp | unknown | rs28362731 | 0.04309 | CO*02 | ||||
| Cob- (including mod phenotypes) | |||||||||
| 1 | Co(a+b+) | Co(a+b−) | c.134 C/T | 45 Ala / Val | Coa+ / Cob+ | rs28362692 | 0.03976 | CO*01 / CO*02 | no cause identified |
| Elution pos | |||||||||
| Cob weak | |||||||||
| 1 | Co(a+b+) | Co(a+wb+) | c.134 C/T | 45 Ala / Val | Coa+ / Cob+ | rs28362692 | 0.03976 | CO*01 / CO*02 | no cause identified |
| 1 | Co(a+b+) | Co(a+b+w) | c.134 C/T; | 45 Ala / Val; | Coa+ / Cob+; | rs28362692 | 0.03976 | CO*01 / CO*02. | p < 0.01 |
| Elution pos | c.502 G/A | 168 Ala / Thr | unknown | - | absent. | (c.502A)† | |||
| False-negative antigen prediction | |||||||||
| 1 | Co(a−b+) | Co(a+) | c.134 C/T; | 45 Ala / Val; | Coa+ / Cob+; | rs28362692 | 0.03976 | CO*01.(c.135A)† / | yes: c.135G>A interferes |
| c.135 G/A | (silent) | - | rs781356338 | 0.00004542 | CO*02 | with primer binding | |||
NC = Not covered (polymorphism outside the scope of ExAC, e.g. in the promoter); absent = no single case worldwide observed in ExAC despite coverage of the region.
*
Frequency of the mutation among non-Finnish Europeans according to the ExAC database (http://exac.broadinstitute.org). If the mutation was absent among non-Finnish Europeans but present wordwide, the worldwide frequency was given with a prefixed W. The mutations possibly causing the discrepancy are indicated by bold letters.
†
Previously unknown allele.
§
The shown polymorphism are frequent and unlikely to cause the discrepant phenotype.