rs17002852 — CYP2D6

Synonymous CYP2D6 variant that causes allele dropout in standard CYP2D6*3 genotyping assays, potentially masking co-inherited non-functional alleles

See your personal result for CYP2D6

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

The CYP2D6 Genotyping Blind Spot

About 25% of all prescription medications are processed by the CYP2D6 enzyme — a figure that spans everything from opioids like codeine and tramadol to antidepressants, antipsychotics, beta-blockers, and tamoxifen. Accurate genotyping of CYP2D6 is therefore one of the highest-stakes tasks in clinical pharmacogenomics. The rs17002852 variant sits in a unique position: it doesn't alter CYP2D6 enzyme function directly, but it can disrupt the diagnostic tools used to read your CYP2D6 status — specifically the detection of the CYP2D6*3 non-functional allele.

The Mechanism

CYP2D6 is located on chromosome 22 (minus strand), and rs17002852 corresponds to a synonymous change11 synonymous change
NM_000106.6:c.696T>C; plus-strand A>G at chr22:42128321 (GRCh38) at codon 696 of the CYP2D6 transcript. The amino acid at position 232 (histidine) remains unchanged — so enzyme structure and activity are unaffected by this variant alone.

The problem arises in the laboratory. Standard hydrolysis probe assays and pyrosequencing assays for CYP2D6*3 (rs35742686)22 CYP2D6*3 (rs35742686)
*3 is a frameshift deletion that abolishes CYP2D6 function are designed around the assumption that the nucleotide at the g.2470 position (rs17002852) is the common reference (A on the plus strand, T on the coding strand). When the G allele is present at rs17002852, its proximity to the *3 detection probe causes allele dropout33 allele dropout
Allele dropout: one allele in a heterozygous sample fails to amplify or be detected, producing a false homozygous result — the affected allele is simply not detected. A person who carries CYP2D6*3 on the same chromosome as rs17002852 G may appear homozygous normal on standard assays, when they are actually a CYP2D6*3 heterozygote or compound heterozygote.

The Evidence

Scantamburlo et al. (2017)44 Scantamburlo et al. (2017)
Allele Drop Out Conferred by a Frequent CYP2D6 Genetic Variation. Cell Physiol Biochem, 43:2297–2309. genotyped 365 patient samples using three parallel methods — Sanger sequencing (gold standard), hydrolysis probe assays, and pyrosequencing. A discrepancy emerged for CYP2D6*3 detection in one sample that also carried rs17002852. The G allele frequency was 2.47% in this cohort, consistent with the global ALFA frequency of 0.74% and higher frequencies observed in Ashkenazi Jewish (~1.7%) and South Asian (~1.8%) populations. The solution was assay redesign to avoid the g.2470 position. The authors recommend intra-patient validation with at least two independent methods when rs17002852 is detected, as any single-method CYP2D6 panel may silently miss a co-inherited *3 or other nearby non-functional allele.

ClinVar records the A>G variant VCV00082887655 VCV000828876
ClinVar drug response classification, single submission, no assertion criteria under a "drug response" classification related to tramadol metabolism — reflecting that misclassification of *3 carrier status would affect tramadol prescribing decisions, since CYP2D6*3 carriers have reduced conversion of tramadol to its active O-desmethyltramadol metabolite.

Practical Actions

Most people carrying the G allele at rs17002852 will never know they have it, and this variant itself does not change how medications work in the body. The actionable implication applies when you are undergoing CYP2D6 genotyping for clinical or pharmacogenomic purposes: standard single-method panels may miss a co-inherited CYP2D6*3 allele. If your genotyping results show this variant alongside CYP2D6*3 detection, or if you are prescribed medications with narrow therapeutic windows where CYP2D6 status matters (tramadol, codeine, tamoxifen, tricyclic antidepressants), confirmatory testing with an alternative method such as next-generation sequencing or a redesigned assay is warranted.

Interactions

This variant's clinical relevance is entirely defined by its interaction with the CYP2D6*3 allele (rs35742686). The rs17002852 G allele can occur in trans (on the opposite chromosome) from CYP2D6*3, or in cis (on the same chromosome), either combination causing the same diagnostic assay problem. Users who carry both rs17002852 G and a CYP2D6 non-functional allele on standard panels should confirm their complete CYP2D6 status with extended genotyping. See also rs3892097 (*4) and rs1065852 (*10) for the full CYP2D6 picture.

Drug Interactions

tramadol dose_adjustment literature

Genotype Interpretations

What each possible genotype means for this variant.

AA No Assay Interference Normal

Standard CYP2D6 genotyping assays will work reliably

The rs17002852 G allele is a synonymous variant (no amino acid change) that sits near the CYP2D6*3 assay probe binding site. Without this G allele, there is no risk of probe interference at this position, and standard CYP2D6 genotyping methods will correctly detect CYP2D6*3 if it is present.

Your CYP2D6 metabolizer status is determined by your other CYP2D6 variants, not this one. See related SNPs rs3892097 (*4) and rs1065852 (*10) for your primary CYP2D6 metabolizer status.

AG Assay Interference Risk Intermediate

May cause allele dropout in CYP2D6*3 detection assays

Because this variant is synonymous, it has no direct effect on how CYP2D6 metabolizes medications. The concern is diagnostic: if you also carry CYP2D6*3 (rs35742686) on the same or the opposite chromosome, standard assays may fail to detect the *3 allele, leaving you with an incomplete metabolizer status assessment.

CYP2D6*3 is a frameshift deletion that completely abolishes enzyme function. Failing to detect it means a potential poor or intermediate metabolizer could be misclassified as a normal metabolizer — a clinically significant error for prescribing decisions involving tramadol, codeine, tamoxifen, and tricyclic antidepressants.

Scantamburlo et al. (2017, PMID 29073588) showed that redesigning CYP2D6*3 assays to avoid the g.2470 position resolves the dropout problem. Modern next-generation sequencing (NGS)-based pharmacogenomics panels are not susceptible to this specific probe interference issue.

GG High Assay Interference Risk High Risk

Rare homozygous state with high risk of CYP2D6 assay misclassification

The homozygous GG genotype is extremely rare (estimated ~0.005% globally based on Hardy-Weinberg from the ~0.74% G allele frequency). At this genotype, both chromosomes carry the G allele at rs17002852, meaning both copies of CYP2D6 will cause probe binding interference in standard assays. Any additional CYP2D6 variants (including *3, *4, or others) on either chromosome are at risk of being missed.

Because the GG state is so rare, it has not been specifically studied in published literature. The inference of high assay interference risk is derived from the established mechanism documented for the AG state (PMID 29073588), scaled for the homozygous condition.

This variant itself does not make you a poor or intermediate CYP2D6 metabolizer. Your actual metabolizer status depends on your other CYP2D6 alleles, which must be assessed by an NGS-based method.