PMS2 Gene — Lynch syndrome caused by PMS2 has lower cancer penetrance than MLH1 or MSH2, but the pseudogene PMS2CL makes standard genetic testing unreliable, and WGS provides more accurate evaluation.
Whole genome sequencing evaluates PMS2 with improved accuracy over panel testing by reading through the complex PMS2/PMS2CL pseudogene region — distinguishing true pathogenic variants from pseudogene sequences.
PMS2 Gene — Lynch Syndrome
PMS2 (chromosome 7p22.1) encodes a DNA mismatch repair protein. Pathogenic PMS2 variants cause Lynch syndrome with lower penetrance than MLH1/MSH2 — approximately 15-20% lifetime CRC risk and 15% endometrial cancer risk (vs. 50-80% CRC for MLH1/MSH2). Despite lower penetrance, PMS2-Lynch still confers clinically significant cancer risk requiring enhanced surveillance.
PMS2 has a unique testing challenge — the pseudogene PMS2CL shares >98% sequence identity with PMS2 exons 1-5, causing variant misassignment in standard next-generation sequencing panels. Variants in the pseudogene may be incorrectly called as PMS2 pathogenic variants (false positives), or true PMS2 variants may be dismissed as pseudogene artifacts (false negatives). Long-range PCR, gene-specific amplification, or whole-genome approaches improve accuracy.
PMS2-Lynch management includes colonoscopy every 1-2 years from age 25-30 (later than MLH1/MSH2 due to lower penetrance), endometrial cancer surveillance for female carriers, and consideration of aspirin chemoprevention. Immunotherapy for PMS2-deficient cancers is highly effective — MSI-high/dMMR tumors respond dramatically to pembrolizumab regardless of which MMR gene is deficient.
PMS2 pseudogene PMS2CL confounds standard genetic testing. Variants are frequently misclassified. If you've had PMS2 'VUS' or 'pathogenic' results from panel testing, WGS confirmation is recommended.
PMS2 is the hardest Lynch gene to test accurately due to its pseudogene. WGS provides superior evaluation by reading the full genomic context, reducing false positives and negatives from pseudogene interference.
Pseudogene interference causes PMS2 false positives and negatives — WGS resolves the ambiguity
Standard NGS panels frequently misassign variants between PMS2 and PMS2CL. A patient told they have a PMS2 pathogenic variant may actually have a benign pseudogene variant (false positive → unnecessary surveillance). Conversely, a true PMS2 variant may be filtered as pseudogene noise (false negative → missed Lynch diagnosis). WGS reads the full genomic context, improving variant assignment accuracy.
PMS2-Lynch cancers respond to immunotherapy — dMMR status unlocks pembrolizumab regardless of the specific MMR gene
PMS2-deficient tumors are MSI-high and respond to immune checkpoint inhibitors. Pembrolizumab is FDA-approved for all MSI-high/dMMR cancers regardless of tissue of origin. Confirming PMS2 germline status identifies the molecular mechanism underlying MSI-high status and triggers cascade family testing.
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.
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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.
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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 PMS2 Gene — Lynch Syndrome 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
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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
