Pharmacogenetics

Star alleles group variants that have been assigned a function for a particular gene. The two alleles can be reported as a diplotype and, where the current nomenclature supports it, used to infer an activity or metaboliser class. The implications are gene- and drug-specific: CYP2C19 variants, for example, can affect clopidogrel activation; CYP2D6 phenotypes are relevant to codeine conversion. An assignment can remain uncertain when variants are not adequately covered or phased.

Some pharmacogenes are technically challenging. For CYP2D6, high sequence similarity to the CYP2D7 pseudogene, as well as copy-number changes and hybrid structures, complicates short-read analysis. A list of individual variants can therefore miss important information about phase and gene copy number. Results should be read together with the reported quality and coverage.

Genome uses Aldy to analyse selected star alleles and PharmCAT to connect pharmacogenetic results with curated recommendations. The tools require different inputs; not every gene or structural variant can be reliably resolved from every sequencing file. The report should therefore be read as a technical analysis with sources, software versions and stated limitations. It does not replace clinical confirmation or review of the underlying guideline.

Pharmacogenetic guidelines relate particular genotype or phenotype classes to specific medicines. Depending on the evidence, they may recommend a dose adjustment, an alternative medicine or no change. Age, co-medication, organ function, indication and other clinical factors still matter. A database annotation is not an individual prescription; treatment decisions belong in clinical care.