Table 4. Genetic defects identified in the different families with thrombocytopenia, affecting the ITGA2B or the ITGB3 genes.
| Families | Gene (region) | Variants | Protein region | Frequency in gnomAD database | Classification (according to the ACMG guidelines) and applicable criteria | Reference | |
|---|---|---|---|---|---|---|---|
| DNA | Protein | ||||||
| 1, 2, 3 | ITGA2B(exon 30) | NM_000419.4:c.3076C>T | p.(Arg1026Trp) p.(Arg995Trp)# | C-terminal cytoplasmic region, conserved site | Not listed | Pathogenic (by legacy) | [19] |
| 4 | ITGA2B(exon 30) | NM_000419.4:c.3077G>A | p.(Arg1026Gln)p.(Arg995Gln)# | C-terminal cytoplasmic region, conserved site | ALL: 0.00040% | Pathogenic (by legacy) | [15] |
| 5 | ITGA2B(exon 29) | NM_000419.4:c.3020G>T | p.(Gly1007Val)p.(Gly976Val)# | Integrin alpha chain, transmembrane | Not listed | VUS(PM2, PP1, PP2, PP3) | New |
| 6 | ITGB3 (exon 14) | NM_000212.2:c.2236A>C | p.(Thr746Pro)p.(Thr720Pro)# | Integrin beta subunit, cytoplasmic | Not listed | VUS(PM2, PP1, PP2, PP3) | New |
| 7 | ITGB3(exon 14) | NM_000212.2:c.2243A>C | p.(His748Pro)p.(His722Pro)# | Integrin beta subunit, cytoplasmic | Not listed | VUS(PM2, PP1, PP2, PP3) | New |
| 8, 9 | ITGB3(exon 14) | NM_000212.2:c.2278C>T | p.(Arg760Cys)p.(Arg734Cys)# | Integrin beta subunit, cytoplasmic | Not listed | Likely-pathogenic(PS4, PM2, PP1, PP2, PP3) | New |
| 10 | ITGB3(exon 14) | NM_000212.2:c.2245G>C | p.(Asp749His)p.(Asp723His)# | Integrin beta subunit, cytoplasmic | Not listed | Pathogenic (by legacy) | [31] |
Abbreviations: ACMG, American College of Medical Genetics and Genomics; PM2, Pathogenic Moderate criteria 2; PP1, Pathogenic Supporting criteria 1; PP2, Pathogenic Supporting criteria 2; PP3, Pathogenic Supporting criteria 3; PS4, Pathogenic Strong criteria 4; VUS, variant of unknown significance.
# In terms of legacy, we included the description of variants used for previous publications, where the signal peptide sequences (31 residues for αIIb and 26 residues for β3) was included.