This page is meant to help families understand the language used in genetic reports. It is not meant to interpret any individual result or provide medical guidance. Genetic results should always be reviewed with your child's genetics team, who can explain what a specific finding may or may not mean in context.
Interactive guide
Walk Through a Sample Report
Click any row to see what it means in plain language. Fields with multiple possible values show all the options your report might contain.
Sample Genetic Test Report
Clinical Whole Exome Sequencing
Report Date: XX/XX/XXXX
Accession: SAMPLE-00000
This field names the gene where the lab identified a change. SETD5 is a gene located on chromosome 3 at position 3p25.3. It provides instructions for making a protein involved in how other genes are regulated during development. When a report lists SETD5, it means the lab found a change in or involving this gene. Your genetics team can explain what the specific finding means in your child's case.
Variant
c.2025_2026delAG (p.Gly676Valfs*2)
This field shows the specific notation used to describe the change found. The c. notation describes the location of the change within the DNA sequence. The p. notation describes the predicted effect on the protein. These are standard formats used in genetics reporting. This notation is the key identifier when searching databases like ClinVar or speaking with a genetic counselor.
This field describes what kind of change was found. Most families are told their child has one of three things:
- Mutation — a change in the DNA sequence.
- Deletion — missing genetic material.
- Duplication — extra genetic material.
Types of genetic changes seen in SETD5
Frameshift Mutation
A change that shifts how the gene's code is read. This term means one or more DNA letters were added or removed in a way that alters the reading frame of the sequence.
Nonsense Mutation
A change that creates an early stop signal in the DNA sequence. This term means a single DNA letter changed in a way that introduces a premature stop codon.
Missense Mutation
A change in which one DNA letter is substituted for another, altering the amino acid specified at that position in the protein sequence.
Splice-site Mutation
A change that may affect how the gene is put together. This term means a change occurred at a boundary where sections of the gene's instructions are joined during protein production.
Deletion Deletion
Missing genetic material. This term means a portion of the DNA sequence is absent. A deletion can be small (a few letters) or large (a section of chromosome). Larger deletions may involve more than one gene.
If your report shows a 3p25 chromosomal deletion, see what that means for SETD5 Syndrome.
Duplication Duplication
Extra genetic material. This term means a section of the DNA sequence is present more than once.
Reports involving SETD5 may describe sequence variants within the gene or deletions involving the gene. The report itself, along with the ordering genetics team, is the best source for understanding which type of result was found in a specific case.
Classification
Likely Pathogenic
This field shows the lab's assessment of the clinical significance of the change found, using a five-tier system defined by the American College of Medical Genetics (ACMG). This classification describes the strength of evidence in the scientific literature — it is not a clinical diagnosis. Your genetics team can explain what the classification means in your child's case.
The five classification levels
Pathogenic
A lab uses this term when there is strong evidence from multiple sources that a variant is associated with disease. This is the highest-confidence classification.
Likely Pathogenic
A lab uses this term when there is strong but not definitive evidence that a variant is associated with disease. Your genetics team can explain what this means in your child's case.
Variant of Uncertain Significance (VUS)
A lab uses this term when there is not yet enough evidence to classify the variant as either disease-causing or benign. This classification can change over time as more data is collected.
Likely Benign
A lab uses this term when the available evidence suggests a variant is unlikely to cause disease.
Benign
A lab uses this term when a variant is not associated with disease based on available evidence and is common in the general population.
Inheritance
De novo (autosomal dominant)
This field describes whether the change was also present in a parent's sample at the time of testing. Not all reports include this field — it depends on whether parental samples were tested. Your genetics team can explain what the inheritance finding means for your family.
Inheritance terms you may see
De novo
This term means the change was not detected in either parent's sample at the time of testing. It does not appear to have been inherited.
Inherited (autosomal dominant)
This term means one parent was also found to carry the same change. Your genetics team can explain what this means for your family.
Unknown / Not tested
This term appears when parental samples were not tested as part of the analysis, so the origin of the change could not be determined.
This field describes how many copies of a gene carry the reported change. Most people have two copies of each gene, one from each parent.
Zygosity terms
Heterozygous
This term means one copy of the gene has the reported change and one does not.
Homozygous
This term means both copies of the gene carry the same change.
Hemizygous
This term means only one copy of the gene is present, rather than the usual two. Your genetics team can explain whether this applies to your child's result.
ACMG Criteria
PVS1, PM2, PP3
This field lists the specific evidence codes the lab used to arrive at the classification. Each code represents one category of evidence from the ACMG guidelines. These codes are primarily intended for clinicians and genetic counselors. Definitions of common codes:
PVS1
The variant causes loss of gene function - a strong indicator of pathogenicity for genes where loss-of-function is a known disease mechanism.
PM2
The variant is absent or extremely rare in population databases like gnomAD, meaning it's not a common harmless variation.
PP3
Computer algorithms predict the variant is damaging to the protein. This is supporting evidence, not a standalone determination.
↑ Click any row to expand - fields with multiple options show all possibilities
This is a sample report for educational purposes only. It does not represent any individual's actual genetic test results.
Variable expression
Why Every Person with SETD5 Syndrome Looks Different
Variable expressivity describes the fact that the same genetic change can cause a wide range of outcomes. Two people in the same family with the identical SETD5 variant can have very different experiences: one might have relatively mild learning differences, while another has more significant support needs across multiple areas.
Genetic background plays a major role. Each person carries roughly 20,000 genes that all interact with one another. These other genes (sometimes called "modifier genes") can influence how SETD5 Syndrome shows up, which is part of why no two children look exactly alike. Your child's unique combination of genes from both parents shapes their outcome in ways researchers are still working to understand.
Variant type and location are areas of active research. The relationship between where in the SETD5 gene a change occurs and its effects is not yet well-understood. Your genetics team can explain what is currently known about the specific variant in your child's report.
Where the research lives
A Guide to Genetics Databases
These are the databases researchers, genetic counselors, and clinicians use. You do not need to use them. But if you want to look up your child's specific variant, here is what each one does.
Databases You May Already Know
- OMIM (omim.org) -- The reference encyclopedia for genetic conditions. Look up "SETD5" or "MRD23" (an older designation for SETD5 Syndrome) for clinical description, research history, and bibliography.
- ClinVar (ncbi.nlm.nih.gov/clinvar/) -- Database of genetic variants and classifications. Search "SETD5" to see all reported variants and which labs submitted them.
- GeneCards (genecards.org) -- Broad summary of what SETD5 does, where it's active, and associated diseases.
- PubMed (pubmed.ncbi.nlm.nih.gov) -- World's largest database of published medical research. Search "SETD5" for all published papers.
Additional Databases Worth Knowing
- DECIPHER (deciphergenomics.org) -- Collects information about people with genomic changes, especially deletions and duplications. If your child has a deletion, DECIPHER may show similar cases.
- ClinGen (clinicalgenome.org) -- Evaluates clinical evidence for specific genes. Their gene curation reports assess which genes can cause problems if a person has too little or too much of the protein they produce.
- gnomAD (gnomad.broadinstitute.org): A large public database of genetic variants from hundreds of thousands of people. If a variant appears frequently here, that is one piece of evidence it may be harmless. If it is rare or absent, that can support (but does not confirm) that it may be disease-causing. Variant interpretation should always be done by a genetics professional.
- MedGen (ncbi.nlm.nih.gov/medgen/) -- Pulls together information from multiple sources into one searchable interface.
- MedlinePlus Genetics (medlineplus.gov/genetics/) -- The most parent-friendly resource. Written by NIH specifically for patients and families.
Support available
Getting Help Understanding Your Report
- Simons Searchlight Genetic Counseling (simonssearchlight.org) -- At the time this page was last updated, enrolled SETD5 families could access board-certified genetic counselors at no cost. Check their website for current offerings.
- MedlinePlus Genetics (medlineplus.gov/genetics/) -- Step-by-step guides explaining genetic test reports.
- National Human Genome Research Institute (genome.gov) -- Educational resources including a genetics glossary.
- National Society of Genetic Counselors (nsgc.org) -- Find a genetic counselor near you.
Free genetic counseling available
At the time this page was last updated, families enrolled in Simons Searchlight could access free genetic counseling. Many families find this to be a helpful resource. A genetic counselor can walk you through your child's specific report and answer questions that no website can. Check the Simons Searchlight website for current availability.
Want a broader overview? For a comprehensive look at what SETD5 Syndrome is and how it affects development, see our Understanding SETD5 Syndrome page.