Variant Annotations
PharmGKB variant annotations provide information about variant-drug pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.
Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.
There are 1 annotations for this variant. Register or sign in to see them.
VIP Variant in CYP2D6
CYP2D6 2988G>A is an intronic polymorphism that has been shown to be associated with aberrant splicing of CYP2D6 [Articles:17112815, 17001295]. This splicing defect leads to the omission of exon 6 from some of the transcribed RNA, and leads to a reduction in activity. CYP2D6 2988G>A is diagnostic of the haplotype CYP2D6*41, which is believed to be responsible for the IM phenotype in the majority of Caucasians [Article:15289790].
Note: The CYP2D6 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.
Appendix
| Genomic Variant & GenBank ID: | G4607A on M33388 |
|---|---|
| mRNA Variant & GenBank ID: | A775 del on X08006 |
| Protein Variant & GenBank ID: | splicing defect |
| GoldenPath Position: | chr22:40853749 on hg 18 |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): | GM17113 |
| DNA Source Containing Heterozygous Reference Allele (Coriell Lines): | GM17205 |
| Key Haplotypes: | CYP2D6*41 |
Connected Drugs
Connected Diseases
| Evidence | Disease |
|---|---|
| Breast Neoplasms | |
| Cystic Fibrosis | |
| Depression | |
| Hypertension | |
| Neoplasms | |
| Pain | |
| Parkinson Disease | |
| Schizophrenia |
Publications related to rs28371725 at chr22:42523805: 4
| Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007. Schroth Werner, et al. [Article:18024866@PubMed] | |
| The 2988G>A polymorphism affects splicing of a CYP2D6 minigene. Clinical pharmacology and therapeutics. 2006. Rau Thomas, et al. [Article:17112815@PubMed] | |
| Impaired expression of CYP2D6 in intermediate metabolizers carrying the *41 allele caused by the intronic SNP 2988G>A: evidence for modulation of splicing events. Pharmacogenetics and genomics. 2006. Toscano Claudia, et al. [Article:17001295@PubMed] | |
| A novel intronic mutation, 2988G>A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects. Clinical pharmacology and therapeutics. 2004. Raimundo Sebastian, et al. [Article:15289790@PubMed] |
Cross-References
- UCSC Golden Path:
- chr22:42523805
- dbSNP:
- rs28371725
- ALFRED:
- SI015498B