Table 4.
Potential novel African ancestry CYP2D6 star alleles inferred from short‐read high‐coverage whole genome sequence data
| Haplotype | Background allele | Additional core variant(s) | Variant type | Count | Country / data seta |
|---|---|---|---|---|---|
| 1 | *1 | rs140900383∼7471C>T | Missense (A226V) | 1 | Gambia (1000G) |
| 2 | *1 | rs141756339∼9164G>A | Missense (R474Q) | 1 | Nigeria |
| 3 | *1 | rs565013903∼7600G>A | Missense (R269P) | 3 | Namibia (SGDP) |
| 4 | *1 | rs567606867∼7004G>A | Missense (E215K) | 1 | Sierra Leone (1000G) |
| 5 | *2 | rs368858603∼7610_7611insT | Frameshift (T272TX) | 2 | Botswana; Kenya (1000G) |
| 6 | *2 | rs368858603∼7610_7611insT + rs374616348∼6628G>T | Frameshift/stop‐gained (T272TX) + Missense (V119L) | 2 | Cameroon; Congo (SGDP) |
| 7 | *2 | rs28371704∼6002A>G + rs28371703∼5992C>A | Missense (H94R, L91M) | 1 | Kenya (1000G) |
| 8 | *2 | rs375715419∼9115A>G | Missense (T458A) | 1 | Zambia |
| 9 | *2 | rs376636053∼6655T>C | Missense (W128R) | 1 | Sierra Leone (1000G) |
| 10 | *2 | rs769157652∼8873G>A | Missense (E410K) | 1 | Sierra Leone (1000G) |
| 11 | *17 | rs747089665∼8885C>T + rs769157652∼8873G>A | Missense (R414C, E410K) | 1 | South Africa |
| 12 | *17 | rs1450231864∼8231T>C | Missense (M347T) | 1 | South Africa (SGDP) |
| 13 | *29 | rs76802407~6012C>Gb | Missense (D97E) | 5 | Burkina Faso, Ghana; Gambia, Sierra Leone (1000G) |
| 14 | *29 | rs201006451∼6767C>T | Missense (A165V) | 1 | Nigeria (1000G) |
| 15 | *29 | rs536109057∼5173C>T | Stop‐gained | 2 | Gambia (1000G) |
| 16 | *29 | rs760940331∼9096G>A | Missense (M451I) | 2 | Gambia (1000G), Nigeria (1000G) |
| 17 | *41 | rs141824015∼8206A>C | Missense (I339L) | 4 | Kenya (1000G), South Africa |
| 18 | *45 | rs3915951∼8177G>T | Missense (R329L) | 2 | Gambia (1000G) |
| 19 | *70 | rs16947∼7870C>Tc | Missense (R296C) | 5 | Cameroon, South Africa |
SGDP, Simons Genome Diversity Project; 1000G, 1000 Genomes Project.
IDs for Coriell and SGDP samples are provided in Supplementary Materials S3 as these samples can potentially be used as reference materials.
This haplotype has recently been validated by Gaedigk et al. 7 —see published haplotype at https://www.pharmvar.org/gene/CYP2D6. Confirmatory submissions to PharmVar for the suballeles identified in this study are ongoing.
Matimba et al. 16 identified CYP2D6*70 (moderate evidence on PharmVar) in their study. In our analysis and laboratory validation, we found that individuals with the *70‐defining variants also had 7870C>T (R296C) in cis.