PALB2 Hereditary Breast Cancer — a high-penetrance breast cancer gene only recently reclassified, meaning thousands of patients received BRCA-negative results before PALB2 was added to standard panels.
Whole genome sequencing reads PALB2, BRCA1, BRCA2, and all ACMG-recommended hereditary cancer genes simultaneously — including patients who tested BRCA-negative years before PALB2 was recognized as a high-penetrance gene.
PALB2 Hereditary Breast Cancer Risk
PALB2 (partner and localizer of BRCA2) encodes a protein that functions as a molecular bridge linking BRCA1 to BRCA2 in the DNA damage response and homologous recombination pathway. Biallelic PALB2 pathogenic variants cause Fanconi anemia complementation group N — a severe bone marrow failure and cancer predisposition syndrome. Monoallelic (heterozygous) PALB2 pathogenic variants confer substantially elevated breast cancer risk. A landmark collaborative study published in the New England Journal of Medicine (2014) and confirmed by subsequent meta-analyses established an average cumulative lifetime breast cancer risk of approximately 35% for PALB2 pathogenic variant carriers overall, rising to 58% in carriers with a family history of breast cancer — effectively equivalent to BRCA2 in terms of penetrance.
PALB2 was formally reclassified as a high-penetrance breast cancer gene in 2014. This reclassification has direct clinical implications for all BRCA-negative patients who were tested under the prior paradigm when PALB2 was categorized as moderate-penetrance: patients who underwent hereditary breast cancer testing before 2015 may have an entirely negative-reported result that predates PALB2 high-penetrance recognition. PALB2 pathogenic variants also elevate ovarian cancer risk (estimated lifetime risk approximately 5-8%, lower than BRCA1/2) and pancreatic cancer risk. Male PALB2 carriers have elevated breast cancer risk.
Clinical management of PALB2 pathogenic variant carriers is evolving. Current NCCN guidelines (2024) recommend annual breast MRI with contrast beginning at age 30 for PALB2 carriers, with consideration of risk-reducing mastectomy based on family history and estimated lifetime risk. Carriers with a strong family history of breast cancer and lifetime risk approaching BRCA2-equivalent levels may be offered risk-reducing surgery under shared decision-making. PALB2 carriers with breast cancer may derive benefit from PARP inhibitor therapy — the therapeutic hypothesis underpinning several ongoing clinical trials, given PALB2's function in the BRCA1/2 homologous recombination pathway.
Patients who tested BRCA-negative before 2015 may never have been tested for PALB2. Standard BRCA-focused panels that added PALB2 later often use limited sequencing approaches that miss structural variants.
A BRCA-negative result is not the same as a negative hereditary breast cancer result
The commercial hereditary cancer testing market was built around BRCA1 and BRCA2. For many years, 'BRCA testing' was the de facto hereditary breast cancer test. PALB2's reclassification as high-penetrance in 2014 created a gap: patients who received BRCA-only results before that date have a formally incomplete hereditary cancer assessment. Additionally, some multi-gene panels added PALB2 after the fact with limited sequencing coverage that does not detect large deletions or deep intronic variants. Whole genome sequencing provides complete PALB2 sequencing as part of a comprehensive hereditary cancer assessment — including all BRCA1/2, PALB2, CHEK2, ATM, and ACMG-recommended cancer genes simultaneously.
PALB2 status informs PARP inhibitor eligibility — a directly actionable clinical decision
Olaparib and talazoparib — PARP inhibitors approved for BRCA1/2-mutated breast cancer — exploit homologous recombination deficiency caused by loss of BRCA1/2 function. PALB2 functions in the same HR pathway, and emerging clinical trial data suggest PALB2 carriers with breast cancer may respond to PARP inhibitor treatment. Ongoing trials including OlympiAD extension cohorts and the PATINA trial are evaluating PARP inhibitors specifically in PALB2-positive patients. Knowing PALB2 status at the time of a breast cancer diagnosis may determine clinical trial eligibility and inform treatment selection — a decision that requires a complete hereditary cancer gene panel result, not a historical BRCA-only test.
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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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.
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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 PALB2 Hereditary Breast Cancer Risk and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
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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
