Table 2.
CYP2D6 Tier 1 Variant Alleles
| Allele | Allele functional status assigned by CPIC† | Core variant(s)‡ | Legacy nomenclature (M33388) ATG start§,¶ | RefSeqGene LRG_303 (NG_008376.4) ATG start§ | RefSeqGene LRG_303 (NG_008376.4) | HGVS genomic nomenclature: GRCh38 (NC_000022.11) | HGVS cDNA nomenclature: LRG_303 (NM_000106.6§) | HGVS protein nomenclature: LRG_303 (NP_000097.3) | Reference material available | Multiethnic allele frequency |
|---|---|---|---|---|---|---|---|---|---|---|
| ∗2 | Normal function | rs16947, rs1135840 | 2850C>T, 4180G>C | 2851C>T, 4181G>C | g.7870C>T, g.9200G>C | g.42127941G>A, g.42126611C>G | c.886C>T, c.1457G>C | p.Arg296Cys, p.Ser486Thr | Yes | 3.9%–29.5% |
| ∗3 | No function | rs35742686 | 2549delA | 2550delA | g.7569del | g.42128242del | c.775del | p.Arg259fs | Yes | <0.1%–1.6% |
| ∗4 | No function | rs3892097 | 1846G>A | 1847G>A | g.6866G>A | g.42128945C>T | c.506-1G>A | (splicing defect) | Yes | 0.5%–18.5% |
| ∗5 | No function | CYP2D6 full gene deletion | Yes | 1.6%–5.4% | ||||||
| ∗6 | No function | rs5030655 | 1707delT | 1708delT | g.6727del | g.42129084del | c.454del | p.Trp152fs | Yes | 0%–1.1% |
| ∗9 | Decreased function | rs5030656 | 2615delAAG | 2616delAAG | g.7635_7637del | g.42128176_42128178del | c.841_843del | p.Lys281del | Yes | 0%–2.8% |
| ∗10 | Decreased function | rs1065852, rs1135840 | 100C>T, 4180G>C | 100C>T, 4181G>C | g.5119C>T, g.9200G>C | g.42130692G>A, g.42126611C>G | c.100C>T, c.1457G>C | p.Pro34Ser, p.Ser486Thr | Yes | 1.4%–43.6% |
| ∗17 | Decreased function | rs28371706, rs16947, rs1135840 | 1023C>T, 2850C>T, 4180G>C | 1022C>T, 2851C>T, 4181G>C | g.6041C>T, g.7870C>T, g.9200G>C | g.42129770G>A, g.42127941G>A, g.42126611C>G | c.320C>T, c.886C>T, c.1457G>C | p.Thr107Ile, p.Arg296Cys, p.Ser486Thr | Yes | <0.1%–19.3% |
| ∗29 | Decreased function | rs59421388, rs61736512+ rs1058164, rs16947, rs1135840 | 3183G>A, 1659G>A, 1661G>C, 2850C>T, 4180G>C | 3184G>A, 1660G>A, 1662G>C, 2851C>T, 4181G>C | g.8203G>A, g.6679G>A g.6681G>C, g.7870C>T, g.9200G>C | g.42127608C>T, g.42525132_42525134delinsGAT, g.42127941G>A, g.42126611C>G | c.1012G>A, c.406_408delinsATC, c.886C>T, c.1457G>C | p.Val338Met, p.Val136Ile, p.Arg296Cys, p.Ser486Thr | Yes | 0%–12.1% |
| ∗41 | Decreased function | rs28371725, rs16947, rs1135840 | 2988G>A, 2850C>T, 4180G>C | 2989G>A, 2851C>T, 4181G>C | g.8008G>A, g.7870C>T, g.9200G>C | g.42127803C>T, g.42127941G>A, g.42126611C>G | c.985+39G>A, c.886C>T, c.1457G>C | N/A (splicing defect), p.Arg296Cys, p.Ser486Thr | Yes | 0.8%–15.4% |
| ×N | Variable, depending the duplicated alleles | Duplications | Yes | Variable |
CPIC, Clinical Pharmacogenetics Implementation Consortium; HGVS, Human Genome Variation Society.
Citations for assignment of function can be found on the Pharmacogene Variation Consortium website (https://www.pharmvar.org, last accessed October 28, 2020); HGVS nomenclature can be found on the National Center for Biotechnology Information website (https://www.ncbi.nlm.nih.gov/snp and http://www.ncbi.nlm.nih.gov/clinvar, both last accessed October 28, 2020).
Core variant(s) can be found on the Pharmacogene Variation Consortium website (https://www.pharmvar.org, last accessed October 28, 2020); the characteristic variant associated with altered function and corresponding HGVS nomenclature for each star allele are underlined.
Count from ATG start site.
The reference sequence initially used for defining variants, M33388, differs from the current RefSeq NG_008376.4 at four positions, of which three are insertion/deletions and thus causes variant coordinates to shift among these reference sequences (https://www.pharmvar.org/gene/cyp2d6, last accessed October 6, 2020). Positions on M33388 are referred to as “legacy.”