A Next-Generation Sequencing (NGS) report is the document created after analyzing a person’s DNA sequence. This technology rapidly reads billions of DNA fragments simultaneously, providing enormous genetic information. The report summarizes these findings, identifying specific differences, or variants, in the individual’s genetic code compared to a reference sequence. Its purpose is to translate complex raw data into a manageable format that informs medical decisions.
Understanding the Report’s Structure
The first page of an NGS report provides a summary and details about the testing methodology used. This section specifies whether the analysis covered a small, targeted group of genes (panel testing), the protein-coding regions (Whole Exome Sequencing or WES), or the entire genome (Whole Genome Sequencing or WGS). Understanding the scope of the test defines the boundaries of the analysis, indicating which parts of the DNA were examined.
A separate section lists the specific genes that were analyzed for the patient. For panel tests, this is a predefined list of genes associated with a particular condition, such as cardiomyopathy or hereditary cancer predisposition. If the test was a broader WES or WGS, the reporting laboratory may focus only on genes relevant to the patient’s symptoms, though the full data set exists in the background.
Reports also include quality metrics, which quantify the reliability of the sequencing process. One frequently cited metric is “coverage,” which indicates how many times, on average, each segment of DNA was read during sequencing. High coverage, often expressed as a numerical value like 50x or 100x, generally suggests the data is more robust and less likely to contain technical errors.
Poor coverage in certain areas, known as “coverage gaps,” means the sequence data for those specific regions may be unreliable or missing entirely. The report details these technical limitations before moving on to the actual genetic findings.
Decoding Variant Classifications
The core of the NGS report is the list of identified genetic variants, each assigned a classification based on its believed clinical effect. These classifications follow standardized guidelines established by organizations like the American College of Medical Genetics and Genomics (ACMG). The most definitive categories are Pathogenic and Likely Pathogenic, which describe variants that are known or highly likely to cause disease, respectively.
A Pathogenic classification means the variant has been strongly linked to the disorder in multiple previous studies and is considered causative. This determination often requires that the variant has been observed in multiple unrelated affected individuals and is absent from large, healthy population databases. A Likely Pathogenic variant has substantial evidence supporting a disease-causing role, though not yet enough to meet the highest threshold of certainty.
Both Pathogenic and Likely Pathogenic categories are generally treated the same way for diagnosis and medical planning. They represent a confirmed or near-confirmed genetic cause for the patient’s symptoms or predisposition. These classifications are the basis for making changes to a patient’s medical care plan.
On the opposite end of the spectrum are Benign and Likely Benign classifications. These variants are common differences in the DNA sequence that do not cause disease and are viewed as normal human variation. They are often listed in the report but are typically disregarded in terms of clinical implications, serving mainly as background context for the individual’s genetic landscape.
The most challenging category for patients and clinicians alike is the Variant of Uncertain Significance, or VUS. A VUS is a genetic change for which there is currently insufficient evidence to determine if it is benign or pathogenic. These variants may be unique to the individual or simply too rare for scientists to have thoroughly studied their effect and function.
A VUS does not provide a definitive diagnosis and should not be used to guide medical treatment until further evidence becomes available. Scientific understanding is constantly improving, meaning a VUS may be reclassified years later as either benign or pathogenic. Because of this possibility, these reports may require periodic re-evaluation by the testing laboratory.
Clinical Application of Results
Once a Pathogenic or Likely Pathogenic variant is identified, the report becomes an actionable guide for medical management. One immediate application is specialized screening and surveillance protocols. For instance, a confirmed pathogenic variant in the BRCA1 gene prompts recommendations for earlier and more frequent breast and ovarian cancer screenings, such as annual mammograms and MRIs, beginning at specified ages.
Results can inform preventative measures designed to reduce the risk of future disease development. Individuals with variants associated with familial adenomatous polyposis (FAP) may be advised to undergo prophylactic surgery to remove the colon, significantly reducing their lifetime risk of colorectal cancer. These recommendations are specific to the gene and condition, often referencing established clinical practice guidelines.
Genetic findings also play a role in guiding treatment decisions, particularly in oncology. Certain cancers harbor specific mutations that make them highly responsive to targeted therapies, such as PARP inhibitors for BRCA-mutated cancers. The NGS report provides the necessary molecular detail for oncologists to select the most effective, personalized drug regimen for the patient based on the tumor’s genetic profile.
Beyond the immediate patient care, a confirmed result carries significant implications for family planning and cascade testing. The report helps determine carrier status, informing couples about the risk of passing on a recessive condition to their children. This information may lead to options like preimplantation genetic diagnosis or prenatal diagnosis during future pregnancies.
A pathogenic finding establishes the need for “cascade screening,” where at-risk relatives are notified and offered testing for the specific variant identified in the patient. This process allows relatives to proactively manage their own risks, potentially preventing serious disease. Sharing the report with specialized medical professionals ensures the findings are properly integrated into care.
A finding related to cardiac function necessitates consultation with a cardiologist who specializes in genetic heart conditions, while an oncological finding requires review by a genetic counselor and an oncologist. This multidisciplinary approach ensures the complex genetic information is translated into appropriate clinical action and shared with all relevant providers.
Limitations and Necessary Context
The NGS report has inherent limitations that require careful contextualization. One important concept is incomplete penetrance, which describes situations where an individual carries a pathogenic variant but never develops the associated disease. This variability means a positive result indicates a significantly increased lifetime risk, not an absolute certainty of illness.
Another constraint relates to the technical boundaries of the testing method itself. Even with comprehensive sequencing like WES or WGS, the analysis may miss certain types of genetic variations that are difficult to detect, such as large structural rearrangements or variants located deep within non-coding regions of the genome. These coverage gaps mean a negative report does not definitively rule out a genetic condition, a concept known as residual risk.
Scientific knowledge about the human genome is constantly accelerating, which necessitates the concept of data reanalysis. Over time, new publications may link a previously unclassified VUS to a disease or provide stronger evidence for a variant’s nature. Laboratories periodically re-evaluate the raw data against the newest scientific literature to provide the most current interpretation of the findings.
Because of these complexities and limitations, the NGS report is not a standalone diagnosis. It represents laboratory data that requires interpretation by a qualified healthcare professional. A genetic counselor or specialist integrates the findings with the patient’s personal and family medical history. They provide context, explain the nuances of incomplete penetrance, and guide the patient through the implications for their health and relatives.