Table 5.
Diplotype-level assessment of Aldy v4.4 genotype extraction from clinical WGS.
| Gene | Concordant/Equivalent diplotypes1 | Discordant diplotypes | Detection of additional major star alleles2,3 | Indeterminate diplotypes4 | CYP2D6 Hybrid diplotype calls4 | Total diplotypes compared |
|---|---|---|---|---|---|---|
| CYP2B6 | 63 | 0 | 30 (1) | (1) | N/A | 93 |
| CYP2C8 | 91 | 0 | 3 | 0 | N/A | 94 |
| CYP2C9 | 92 | 1 | 1 | 0 | N/A | 94 |
| CYP2C19 | 84 | 0 | 10 (3) | 0 | N/A | 94 |
| CYP2D6 | 58 | 2 | 26 | 0 | (8) | 87 |
| CYP3A4 | 91 | 0 | 3 | 0 | N/A | 94 |
| CYP3A5 | 94 | 0 | 0 | 0 | N/A | 94 |
| CYP4F2 | 68 | 0 | 26 | 0 | N/A | 94 |
| DPYD | 21 | 0 | 73 (8) | 0 | N/A | 94 |
| G6PD | 94 | 0 | 0 | 0 | N/A | 94 |
| NUDT15 | 0 | 0 | 1 (1) | 0 | N/A | 1 |
| SLCO1B1 | 38 | 0 | 56 (2) | 0 | N/A | 94 |
| TPMT | 87 | 0 | 3 | (4) | N/A | 90 |
| VKORC1 | 94 | 0 | 0 | 0 | N/A | 94 |
| Total | 975 | 3 | 232 (15) | (5) | (8) | 1211 |
1.Alleles with the same tag variant(s) (e.g., CYP2D6*2 versus CYP2D6*34 and CYP2D6*39) were considered as equivalent alleles.
2.Additional clinically actionable star alleles were defined as alleles classified as having increased function, decreased function, or no function within current Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines that were not included on our genotyping reference standard. Since no current CPIC guidelines include CYP2C8 or CYP3A4 genotype-guided recommendations, there was no potential to identify additional clinically actionable star alleles. Diplotypes containing additional clinically actionable star alleles are in parentheses.
3.DPYD no longer uses star allele nomenclature according to PharmVar, so any additional variant called by Aldy for DPYD was interpreted as an additional allele.
4.Values in parentheses were not included in diplotype concordance analysis for subjects with indeterminate diplotypes or CYP2D6 hybrid calls.