Pharmacogenetics - conversion of variants(CYP genes) to CYP diploid allele

Question

[Sarath Kumar]

Hi , I am new this biostar community.

I have a vcf file with variants in CYP genes(Cytochrome p450). i want to convert these variants into diploid allele format(like CYP2D6 1/4 ) for CPIC( Clinical Pharmacogenetics Implementation Consortium) guidline annotation.

Thanks in advance,

Answer 1

[Kevin Blighe]

Have you looked at Pharma GKB? From there, you can download translation tables for many CYP genes, including CYP2D6.

A 'translation table' for CYP2D6 will have, for example, a haplotype on each row and then the variants required to identify the haplotype in each column.

Here are the translation tables for CYP2D6: https://www.pharmgkb.org/gene/PA128/haplotype

[Sarath Kumar]

thanks for your reply, As you said (CYP2D6: https://www.pharmgkb.org/gene/PA128/haplotype) here we can get only haplotype information but my doubt is how to get the diplotype information from variants (CYP2D6 *1/*2, CYP2D6 *2/*2) or without getting diplotype information how can we get metabolizer phenotype (Ultrarapid metabolizer-UM, Intermediate metabolizer - IM , Poor metabolizer -PM and so on)?

[Kevin Blighe]

From what I understand, the information is publicly available through open access journals and other literature.

From your VCF variants, you should be able to identify (manually or otherwise) the CYP2D6 haplotype per patient, and then you can look these up here:

https://www.nature.com/tpj/journal/v7/n4/fig_tab/6500406t1.html#figure-title

..or here:

https://www.snpedia.com/index.php/Drug_Metabolism

[Edit: there are many sources of information publicly available, but I am not sure that there is a single open-access resource that links the haplotypes to the metabolizer phenotype, i.e., the information is interspersed amongst a lot of literature]