Understanding Your Genetic Testing Report: Key Elements for the Shwachman-Diamond Syndrome (SDS) Community and Why it Matters

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Genetic testing reports can seem overwhelming at first glance—especially with all the complex scientific terms and data. But each section of a genetic testing report tells an important part of your or your child’s genetic story.

For families affected by Shwachman-Diamond Syndrome (SDS), understanding these reports is key to making informed medical decisions and contributing to vital research programs/registries like SDS-GPS (Global Patient Survey and Collaboration Program).

Where to Find Your Genetic Testing Report

If you already completed genetic testing, you should be able to access your full report through the provider or platform where the test was ordered. Many genetic testing laboratories offer online patient portals (e.g., GeneDx and Blueprint Genetics), where you can log in and download the report directly. You can also request a copy from the clinician who ordered the test—usually a genetic counselor, hematologist, or pediatrician. If your child was tested years ago, the report may be stored in the hospital’s medical records department, and you can request it through a Records or Health Information office. If you have never received a copy of the full written report, you are fully entitled to one, and having direct access is important for your ongoing care and for contributing to research programs such as the SDS-GPS. If you are having difficulties accessing your report, please reach out to us at genetics@sdsalliance.org for help.

Why a Genetic Diagnosis Matters

While clinical symptoms may strongly suggest SDS, a confirmed genetic diagnosis provides clarity that symptoms alone cannot. Only genetic testing can determine which gene is affected (such as SBDS, DNAJC21, EFL1, or SRP54) and whether the pattern of inheritance fits SDS. This information is crucial for several reasons:

• It ensures the correct diagnosis and avoids misdiagnosis with other bone marrow failure disorders.

• It guides medical surveillance and treatment decisions, especially for monitoring leukemia risk.

• It helps determine recurrence risks for future pregnancies and whether family members should be tested.

• It allows individuals to participate in research programs like the SDS-GPS and clinical trials. A genetic report helps accurately contribute to global SDS knowledge.

Even if SDS is strongly suspected clinically, confirming the diagnosis through genetic testing provides a foundation for precise care, family planning, and research participation.

Why It’s Important to Understand Your SDS Genetic Testing Report

When you know how to read your genetic testing report, you can better:

• Interpret your or your child’s results

• Discuss next steps with your care team

• Decide whether additional testing is needed

• Contribute valuable information to SDS research

• Have an opportunity to participate in research like clinical trials

This understanding is especially important in rare diseases like Shwachman-Diamond Syndrome (SDS), where every result helps improve diagnosis and treatment for the entire community.

Why Getting a Genetic Diagnosis for SDS Matters

While many individuals may show clinical features suggestive of Shwachman-Diamond Syndrome—such as pancreatic insufficiency, low blood counts, or bone marrow abnormalities—a confirmed genetic diagnosis is essential.

Here’s why it matters:

1. Accuracy and Certainty: Clinical symptoms can overlap with other bone marrow failure syndromes or pancreatic disorders. Only genetic testing can fully confirm SDS and identify the exact gene variants responsible, most commonly in the SBDS gene.

2. Personalized Care: A genetic diagnosis guides your healthcare team in developing a tailored care plan, including monitoring for complications like bone marrow failure or leukemia, which may vary depending on the gene involved (e.g., SBDS, DNAJC21, EFL1, or SRP54).

3. Family Planning and Carrier Testing: Knowing the specific variants allows for family member testing, carrier screening, and genetic counseling for future family planning.

4. Access to Research and Support: Many research studies and clinical trials, especially gene therapy and other precision medicine approaches, require a confirmed genetic diagnosis to ensure accurate data and targeted advances in therapy. While not required, a confirmed genetic status makes all research efforts, including SDS-GPS richer and allows for more learning and meaningful conclusions.

5. Community and Advocacy Impact: A confirmed genetic diagnosis strengthens collective research data and improves advocacy for SDS-specific treatments and resources. It also open doors for community support.

Bottom line: If you or your child show symptoms consistent with SDS, genetic testing is the best way to confirm the diagnosis and unlock the most appropriate care and research opportunities.

Key Elements of a Genetic Testing Report

A typical genetic testing report includes several main sections:

1. Patient Information – Basic identifying details such as name and date of birth.

2. Test Details – Which genes were analyzed, the testing method, and the lab performing the analysis.

3. Findings / Results – The specific genetic variants (mutations) identified.

4. Interpretation – What those variants mean for health or diagnosis.

5. Recommendations – Suggested next steps, such as parental or sibling testing.

What Do Genetic Variant Classifications Mean?

Each genetic variant is classified according to how likely it is to cause disease:

• Pathogenic – Proven to cause disease.

• Likely Pathogenic – Strong evidence it causes disease.

• Variant of Uncertain Significance (VUS) – Not enough data to know yet.

• Likely Benign or Benign – Normal genetic differences that do not cause disease.

Note: Most reports only list variants that could be related to disease. Benign variants are rarely included.

Which Genes Are Important in SDS?

In Shwachman-Diamond Syndrome, variants (mutations) in the SBDS gene are the most common cause.

However, other genes may also play a role in causing SDS or SDS-like syndromes, including:

• DNAJC21

• EFL1

• SRP54

Identifying which gene is affected helps confirm the diagnosis and guide clinical care.

Germline vs. Somatic Genetic Testing: What’s the Difference?

Understanding whether your report reflects germline or somatic testing is essential:

Type of Testing	What It Looks At	Purpose	Common in SDS?
Germline Testing	DNA variations you were born with	Diagnoses inherited conditions, such as SDS	✅ Yes — to establish or confirm an SDS diagnosis
Somatic Testing	DNA changes that occur later in life (e.g., bone marrow cells)	Monitors acquired mutations, to monitor blood stem cell health and asses leukemia risk	✅ Yes — to check for changes in the blood stem cells, either using bone marrow samples or peripheral blood. Recommended on a yearly basis or more, if changes are detected.

• Germline reports may include information about whether variants were inherited from parents.

• Somatic reports often list many variants and show the variant allele frequency (VAF) — the percentage of cells carrying each change.

Understanding the type of test helps you interpret what results are most relevant for your family.

Learn more about germline vs. somatic genetic testing in our Ask-an-Expert webinar

Featuring Dr. Lisa McReynolds titled "What are cloned, germline vs. somatic mutations, and why do they matter in SDS?"

Learn more about genetics and what you need to know: Key insights for the Shwachman-Diamond Syndrome Community

We prepared a short overview video to help you get all you need to know.

What Is a “Family Studies” or “Segregation Analysis” Section?

Some reports include family study results, which indicate whether each variant was inherited from one or both parents. This process helps determine phase—whether the two variants are on the same or opposite copies of a gene. If all mutations are on the same copy of the gene, that would leave the other copy to be healthy, and the person would be a carrier rather than having SDS.

In SDS, having two variants on opposite copies of the SBDS gene (one from each parent) is typically required for a confirmed diagnosis.

How Sharing Your Genetic Report Advances SDS Research

By understanding and sharing your results, you contribute directly to SDS research. Uploading your or your child’s report to the SDS-GPS is a meaningful way to participate—you can upload them anytime, or reach out to the GPS team for assistance at gps@sdsalliance.org.

Each report helps researchers:

• Discover possible new SDS-related genes

• Improve genetic testing accuracy

• Develop better treatment strategies

• Give you access to participate in research and clinical trials

Your report can help uncover new insights and accelerate progress for everyone affected by Shwachman-Diamond Syndrome

Frequently Asked Questions (FAQ)

🧬 What does a pathogenic variant mean in SDS?

A pathogenic variant is a genetic change known to cause Shwachman-Diamond Syndrome or another disease. In SDS, these are most often found in the SBDS gene.

🧩 What is a Variant of Uncertain Significance (VUS)?

A VUS means the lab found a change in your DNA, but there isn’t enough scientific evidence yet to determine whether it causes disease. Over time, as more research becomes available, VUS results can be reclassified.

👪 Can parents or siblings be tested for SDS?

Yes. Family testing helps determine whether a variant was inherited and whether other family members may carry the same change. This information can also clarify uncertain results.

🧫 Why might someone with SDS have both germline and somatic test results?

Some people with SDS undergo somatic testing (e.g., on bone marrow) to monitor for genetic changes that might increase the risk of myelodysplastic syndrome or leukemia. This type of surveillance help determine the best timing and type of intervention.

🌍 What is the SDS-GPS program?

The SDS-GPS (Global Patient Survey and Collaboration Platform, a type of Registry) is an international initiative that collects and curates genetic testing reports from people with SDS, in the context of patient/family reported data on how SDS affects them. Sharing your results helps scientists better understand the genetic landscape of SDS and develop improved treatments.

Empowering the SDS Community Through Knowledge

Understanding your SDS genetic testing report empowers you to ask informed questions, advocate for your family, and support life-changing research.

Every report shared and every family engaged helps bring the SDS community one step closer to better diagnostics, care, and cures.

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