Genetic testing is a laboratory test that can help figure out the cause of your child’s health problem or condition by looking for genetic variations associated with a disease. The results are generated as a genetic test report. If you have ever tried to read your child’s genetic test report and found it hard to understand, rest assured you are not alone! We are going to walk you through some examples, so the next time you read one, it will make just a little more sense.
About genes and genetics
Before we get into the details of the genetic test report, let’s talk a little bit about genes and genetics and what types of genetic tests you or your child may have. Genes are the body’s instruction manual. There are thousands of genes (around 20,000 in fact!) that provide the blueprint for building the body, including instructions for eye color, hair color and how the pancreas regulates blood sugar and insulin. And they provide instructions to build proteins in the body.
Genes are made up of a four-letter alphabet: A, T, G, C. Most genes come in pairs, and they’re housed on structures called chromosomes. A common analogy used to describe chromosomes is a beaded necklace, where the beads represent the individual genes, and the necklace is like the chromosome holding those beads:
- We have 46 (or 23 pairs of) chromosomes in almost every cell in our bodies.
- Each person inherits one chromosome from their mother and one from their father, making up each pair of their chromosomes. This means that we have two copies of most of our genes.
- Each individual gene is quite large, often many thousands of letters long (you can think of it as a long gene sentence.)
Thanks to the Human Genome Project and the work of many scientists over the years, we know how genes are supposed to be spelled to correctly build the body. We also know that misspellings in those genes (changes in the gene sentence, commonly referred to as a mutation) can cause things to be built incorrectly or not to get built at all. This can potentially lead to your child having medical problems like hyperinsulinism.
<insert drawings of a gene sequence and chromosome “necklace.” See original document from the BCP>
What does genetic testing do?
The goal of genetic testing is to determine if any genes are misspelled in you or your child. This information can help your child’s doctor understand hyperinsulinism better and be able to tell if there are other health problems for which you or your child need to be checked. Genetic test results can help your child’s care team figure out the best treatment to use. They can also help predict the chances that other family members (including future children) may have hyperinsulinism.
Types of genetic tests
There are many different types of genetic tests available. Common tests include:
- Single gene testing – where we examine one gene
- Gene panel testing – where we look at a group of genes
- Exome or genome sequencing – where we test most of the genes in the body
- Microarrays and chromosome tests (karyotypes) - where we look for large pieces of extra or missing genetic material
Types of genetic test results
Once testing is done, there are three main types of results:
- Positive
- Negative
- Variant of uncertain clinical significance
Positive result – A positive result means the test found a change in a gene that may be linked to hyperinsulinism in your child. Whether this change causes the condition depends on the type of gene. A single gene that causes a trait (dominant gene) can cause hyperinsulinism if just one copy of the gene has a change. If your child has a gene that needs two copies to create changes (recessive gene) they are likely just a carrier and not affected with symptoms.
One rare exception is focal hyperinsulinism, which can happen when a single recessive change from a father combines with other changes during pregnancy.
Negative result - A negative result means the test did not find any relevant changes or misspellings in the genes tested. This result does not rule out a genetic cause of your child's symptoms but does mean a genetic cause has not been found yet.
Variant of uncertain clinical significance (VUS/VOUS): This result means a genetic change was found, but it’s unclear whether it causes disease or is just a normal variation. These uncertain results happen because we don’t yet know all the ways genes can differ without causing problems. Sometimes more testing can help, but in other cases, it may take years to understand what the change means.
Examples of genetic testing results
Let’s look at a few examples of genetic test results.
Positive result example
To figure out how to read this positive result, we have broken it up into seven sections:
1. Gene transcript
This first part of the report shows the name of the gene with the change and the transcript version the lab used to analyze it. The transcript helps your child’s healthcare team interpret the results accurately, but you don’t need to focus on it when reading the report.
2. Mode of inheritance, gene OMIM
The second part of the report lists the types of inheritance linked to the gene (dominant and recessive) but doesn’t specify which applies to this change. The number 600509 is the Online Mendelian Inheritance in Man (OMIM) gene number. OMIM is an online database of genes and associated symptoms in humans.
3. DNA variants, predicted effects and zygosity
This part of the report shows the exact change found in the gene and how it affects the gene's instructions. In this case, one letter in the DNA is different, which creates a stop signal at position 598 and causes the instructions to end too early. It also says the change is heterozygous, meaning it’s only in one of the two copies of the gene. The opposite of heterozygous is homozygous, which means there were two copies of the same genetic change present in your child when they were tested.
4. ClinVar ID
Part four of the report shows the gene change’s number in the ClinVar database, where doctors and genetic testing labs can list genetic misspellings that they find, along with their interpretation of the misspelling. The number listed in this report example (434056) brings you directly to the ClinVar page for this particular ABCC8 gene change.
5. Highest allele frequency in a gnomAD population
Section five tells us how common a genetic change is in a population database called gnomAD. For gnomAD, generally healthy people have volunteered to have their genes tested to help us learn some of the alternative ways genes may be spelled. This report shows us that in the gnomAD database, this ABCC8 gene change has been seen the most in a small percentage of people of African ancestry who are included in this database.
6. In silico missense predictions
This section refers to software programs that predict whether a genetic change is likely to cause a problem with the protein made using the misspelled gene. In this case, the report says “not applicable” because the type of genetic change (essentially a stop sign inserted in the gene) cannot be analyzed with the available software programs.
7. Interpretation
Interpretation refers to whether the lab, based on all available information, believes the genetic change is likely to cause disease or not (pathogenic). Other result interpretations that could appear include:
- Likely pathogenic - likely to cause disease but not 100% certain
- VUS
- Likely benign - most likely not to cause disease but not 100% certain
- Benign – not likely to cause disease
VUS result example
Here’s a breakdown of a genetic report from a different lab that found a VUS result (shown in the “interpretation” portion of the report) in the PMM2 gene (shown in the first part of the report). This means the lab isn’t sure if the genetic change is harmless or if it might cause problems for your child. While the format is different from other reports, it provides similar information. Here are the main points explained in simple terms:
- Nucleotide position (c.539T>C) - Genes are made up of letters, and at position 539, there should be a T (thymine), but it was changed to a C (cytosine). This is a small change in the genetic code.
- Amino acid position (p.Phe180Ser) - Genes give instructions to make proteins, which are made up of building blocks called amino acids. In this case, the 180th amino acid should be F (phenylalanine), but it was changed to S (serine), which could change how the protein works.
- Location - This tells us which part of the gene, called the exon, the change is found in. Exons are the parts of a gene that give the instructions for making proteins.
- Zygosity (heterozygous) - This means only one copy of the gene has the change. Remember, people usually have two copies of each gene—one from their mom and one from their dad.
Negative result example
This report tells us no genetic changes were found when the test was run. This means no pathogenic, likely pathogenic or VUS changes were identified. A negative result does not rule out a genetic cause of your child’s hyperinsulinism, but it does mean a genetic cause has not yet been identified.
Additional report information
Genetic test reports typically contain additional information like a list of all the genes that were part of the test, the version of the genes tested (gene transcript), as well as a description of how the testing was done. This information may be important for your child’s healthcare team to know or reference, but it is information you can typically ignore.
With this information and the examples we’ve shared, you are now ready to read your child’s genetic test report! Still, you may find some parts of the report hard to understand. If you would like to discuss the result of a genetic test further, reach out to the healthcare provider who ordered the test, or our HI genetic counselor for help!
Genetic testing is a laboratory test that can help figure out the cause of your child’s health problem or condition by looking for genetic variations associated with a disease. The results are generated as a genetic test report. If you have ever tried to read your child’s genetic test report and found it hard to understand, rest assured you are not alone! We are going to walk you through some examples, so the next time you read one, it will make just a little more sense.
About genes and genetics
Before we get into the details of the genetic test report, let’s talk a little bit about genes and genetics and what types of genetic tests you or your child may have. Genes are the body’s instruction manual. There are thousands of genes (around 20,000 in fact!) that provide the blueprint for building the body, including instructions for eye color, hair color and how the pancreas regulates blood sugar and insulin. And they provide instructions to build proteins in the body.
Genes are made up of a four-letter alphabet: A, T, G, C. Most genes come in pairs, and they’re housed on structures called chromosomes. A common analogy used to describe chromosomes is a beaded necklace, where the beads represent the individual genes, and the necklace is like the chromosome holding those beads:
- We have 46 (or 23 pairs of) chromosomes in almost every cell in our bodies.
- Each person inherits one chromosome from their mother and one from their father, making up each pair of their chromosomes. This means that we have two copies of most of our genes.
- Each individual gene is quite large, often many thousands of letters long (you can think of it as a long gene sentence.)
Thanks to the Human Genome Project and the work of many scientists over the years, we know how genes are supposed to be spelled to correctly build the body. We also know that misspellings in those genes (changes in the gene sentence, commonly referred to as a mutation) can cause things to be built incorrectly or not to get built at all. This can potentially lead to your child having medical problems like hyperinsulinism.
<insert drawings of a gene sequence and chromosome “necklace.” See original document from the BCP>
What does genetic testing do?
The goal of genetic testing is to determine if any genes are misspelled in you or your child. This information can help your child’s doctor understand hyperinsulinism better and be able to tell if there are other health problems for which you or your child need to be checked. Genetic test results can help your child’s care team figure out the best treatment to use. They can also help predict the chances that other family members (including future children) may have hyperinsulinism.
Types of genetic tests
There are many different types of genetic tests available. Common tests include:
- Single gene testing – where we examine one gene
- Gene panel testing – where we look at a group of genes
- Exome or genome sequencing – where we test most of the genes in the body
- Microarrays and chromosome tests (karyotypes) - where we look for large pieces of extra or missing genetic material
Types of genetic test results
Once testing is done, there are three main types of results:
- Positive
- Negative
- Variant of uncertain clinical significance
Positive result – A positive result means the test found a change in a gene that may be linked to hyperinsulinism in your child. Whether this change causes the condition depends on the type of gene. A single gene that causes a trait (dominant gene) can cause hyperinsulinism if just one copy of the gene has a change. If your child has a gene that needs two copies to create changes (recessive gene) they are likely just a carrier and not affected with symptoms.
One rare exception is focal hyperinsulinism, which can happen when a single recessive change from a father combines with other changes during pregnancy.
Negative result - A negative result means the test did not find any relevant changes or misspellings in the genes tested. This result does not rule out a genetic cause of your child's symptoms but does mean a genetic cause has not been found yet.
Variant of uncertain clinical significance (VUS/VOUS): This result means a genetic change was found, but it’s unclear whether it causes disease or is just a normal variation. These uncertain results happen because we don’t yet know all the ways genes can differ without causing problems. Sometimes more testing can help, but in other cases, it may take years to understand what the change means.
Examples of genetic testing results
Let’s look at a few examples of genetic test results.
Positive result example
To figure out how to read this positive result, we have broken it up into seven sections:
1. Gene transcript
This first part of the report shows the name of the gene with the change and the transcript version the lab used to analyze it. The transcript helps your child’s healthcare team interpret the results accurately, but you don’t need to focus on it when reading the report.
2. Mode of inheritance, gene OMIM
The second part of the report lists the types of inheritance linked to the gene (dominant and recessive) but doesn’t specify which applies to this change. The number 600509 is the Online Mendelian Inheritance in Man (OMIM) gene number. OMIM is an online database of genes and associated symptoms in humans.
3. DNA variants, predicted effects and zygosity
This part of the report shows the exact change found in the gene and how it affects the gene's instructions. In this case, one letter in the DNA is different, which creates a stop signal at position 598 and causes the instructions to end too early. It also says the change is heterozygous, meaning it’s only in one of the two copies of the gene. The opposite of heterozygous is homozygous, which means there were two copies of the same genetic change present in your child when they were tested.
4. ClinVar ID
Part four of the report shows the gene change’s number in the ClinVar database, where doctors and genetic testing labs can list genetic misspellings that they find, along with their interpretation of the misspelling. The number listed in this report example (434056) brings you directly to the ClinVar page for this particular ABCC8 gene change.
5. Highest allele frequency in a gnomAD population
Section five tells us how common a genetic change is in a population database called gnomAD. For gnomAD, generally healthy people have volunteered to have their genes tested to help us learn some of the alternative ways genes may be spelled. This report shows us that in the gnomAD database, this ABCC8 gene change has been seen the most in a small percentage of people of African ancestry who are included in this database.
6. In silico missense predictions
This section refers to software programs that predict whether a genetic change is likely to cause a problem with the protein made using the misspelled gene. In this case, the report says “not applicable” because the type of genetic change (essentially a stop sign inserted in the gene) cannot be analyzed with the available software programs.
7. Interpretation
Interpretation refers to whether the lab, based on all available information, believes the genetic change is likely to cause disease or not (pathogenic). Other result interpretations that could appear include:
- Likely pathogenic - likely to cause disease but not 100% certain
- VUS
- Likely benign - most likely not to cause disease but not 100% certain
- Benign – not likely to cause disease
VUS result example
Here’s a breakdown of a genetic report from a different lab that found a VUS result (shown in the “interpretation” portion of the report) in the PMM2 gene (shown in the first part of the report). This means the lab isn’t sure if the genetic change is harmless or if it might cause problems for your child. While the format is different from other reports, it provides similar information. Here are the main points explained in simple terms:
- Nucleotide position (c.539T>C) - Genes are made up of letters, and at position 539, there should be a T (thymine), but it was changed to a C (cytosine). This is a small change in the genetic code.
- Amino acid position (p.Phe180Ser) - Genes give instructions to make proteins, which are made up of building blocks called amino acids. In this case, the 180th amino acid should be F (phenylalanine), but it was changed to S (serine), which could change how the protein works.
- Location - This tells us which part of the gene, called the exon, the change is found in. Exons are the parts of a gene that give the instructions for making proteins.
- Zygosity (heterozygous) - This means only one copy of the gene has the change. Remember, people usually have two copies of each gene—one from their mom and one from their dad.
Negative result example
This report tells us no genetic changes were found when the test was run. This means no pathogenic, likely pathogenic or VUS changes were identified. A negative result does not rule out a genetic cause of your child’s hyperinsulinism, but it does mean a genetic cause has not yet been identified.
Additional report information
Genetic test reports typically contain additional information like a list of all the genes that were part of the test, the version of the genes tested (gene transcript), as well as a description of how the testing was done. This information may be important for your child’s healthcare team to know or reference, but it is information you can typically ignore.
With this information and the examples we’ve shared, you are now ready to read your child’s genetic test report! Still, you may find some parts of the report hard to understand. If you would like to discuss the result of a genetic test further, reach out to the healthcare provider who ordered the test, or our HI genetic counselor for help!