Codeine & Opioid Response — CYP2D6 variants that convert codeine to morphine at rates ranging from zero to dangerously high, with an FDA black box warning issued after pediatric deaths in ultra-rapid metabolizers.
Whole genome sequencing provides the complete CYP2D6 diplotype — including gene duplication events that create ultra-rapid metabolizer status — for all CYP2D6-substrate opioids: codeine, tramadol, hydrocodone, and oxycodone.
Codeine & Opioid Response — CYP2D6
Codeine is a prodrug that requires metabolic activation by the cytochrome P450 enzyme CYP2D6 to produce its active analgesic metabolite, morphine. The fraction of codeine converted to morphine — and therefore the analgesic effect and toxicity risk — is directly determined by CYP2D6 metabolizer status. CYP2D6 is one of the most polymorphic human genes, with over 100 named star alleles that produce a spectrum of metabolizer phenotypes from complete absence of enzyme activity (poor metabolizers) to dramatically amplified activity (ultra-rapid metabolizers carrying duplicated or multiplied functional gene copies).
CYP2D6 ultra-rapid metabolizers (UMs) — carrying 3 or more functional CYP2D6 gene copies — convert codeine to morphine at supranormal rates, producing morphine plasma levels equivalent to significantly higher doses. This creates a life-threatening risk of respiratory depression, particularly in children. The FDA issued a black box warning on codeine in 2013 and subsequently contraindicated codeine use in all children under 12 and in breastfeeding women after multiple pediatric deaths were attributed to CYP2D6 ultra-rapid metabolism. CYP2D6 poor metabolizers (PMs) carry two loss-of-function alleles and derive essentially no analgesic benefit from codeine — these patients experience no pain relief at standard doses and may be incorrectly labeled 'drug-seeking' when they report inefficacy.
CYP2D6 also mediates the metabolism of tramadol (activated to O-desmethyltramadol), hydrocodone (activated to hydromorphone), and oxycodone (partially metabolized via CYP2D6). The CPIC Level A guideline for codeine and CYP2D6 recommends alternative analgesics for both ultra-rapid and poor metabolizers — eliminating the extremes of the metabolizer spectrum from codeine prescribing. UM frequency varies substantially by ancestry: approximately 1-2% of Northern Europeans, 3-4% of African Americans, and 10-20% or higher in some North African and Middle Eastern populations carry ultrarapid genotypes.
CYP2D6 ultra-rapid metabolizer frequency reaches 10-20% in North African and Middle Eastern populations — a finding with direct safety implications for codeine prescribing in these communities.
CYP2D6 ultra-rapid metabolizer status arises from gene duplication events that standard SNP-based panels and most pharmacogenomics tests cannot reliably detect. Complete CYP2D6 copy number analysis requires genome-level sequencing.
Gene duplication — the variant that kills — requires genome-level copy number analysis to detect
CYP2D6 ultra-rapid metabolizer status most commonly arises from gene duplication or multiplication events where an individual inherits 3, 4, or more copies of a functional CYP2D6 allele. Standard pharmacogenomics panels based on SNP genotyping can identify the major loss-of-function alleles (*3, *4, *5, *6) but have limited and variable ability to detect gene duplications. Multiple validation studies have documented patients classified as 'normal metabolizers' by SNP panels who were subsequently found to carry CYP2D6 gene duplications — ultra-rapid metabolizers who would have been prescribed codeine under the false assumption of normal metabolism. Whole genome sequencing provides both variant identification and copy number analysis across the CYP2D6 locus.
One genome result covers codeine, tramadol, hydrocodone, and every CYP2D6-substrate drug for life
CYP2D6 metabolizes not only codeine and tramadol but also a broad range of medications across multiple drug classes — antidepressants (fluoxetine, paroxetine, venlafaxine), antipsychotics (haloperidol, risperidone), beta-blockers (metoprolol), antiemetics (ondansetron), and tamoxifen. A complete CYP2D6 diplotype from whole genome sequencing provides actionable prescribing information for all of these drugs simultaneously and permanently. The result is generated once and applies to every future prescribing encounter involving a CYP2D6-substrate medication — a lifetime pharmacogenomic asset.
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
Comprehensive insights and specialized reports
Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
Your test becomes more valuable every year
Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
Accredited by & published in
Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Codeine & Opioid Response — CYP2D6 and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
- Custom genomic reports for your members
- Group discounts and tailored packages
- Any country — including virtual groups
- Rare and common conditions covered
Message received.
We'll be in touch within 2 business days. To follow up directly: hello@dantelabs.com
One test.
A lifetime of answers.
One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
