Laboratory Genetic Counseling
Definitions of Commonly-Used Genetic Terms
Medical Genetics and Molecular Pathology feature specialized terminology that constantly changes and evolves with each field.
The list of definitions provided here outlines frequently-used genetics terms and their definitions.
This list is used with permission from the Genomic Medicine Institute’s Center for Personalized Genetic Healthcare at Cleveland Clinic.
One version of a gene or DNA sequence at particular location (locus).
Different genetic changes (variants) in the same gene causing the same or similar phenotype (presentation of symptoms).
A characteristic of some genetic conditions where the disease may present with more severe symptoms and at an earlier age with each generation.
A change in the DNA sequence that does not cause disease or any symptoms. Benign variants, formerly referred to as polymorphisms, tend to be very common in the general population.
A sequence of three DNA or RNA nucleotide bases that correspond to a single amino acid (protein building block).
The presence of two different disease-causing variants, one on each copy of the gene. Generally, one copy is inherited from each parent.
Copy Number Variation (CNV)
A variation in the amount of DNA. DNA is typically present in two copies that are contained on pairs of chromosomes.
Deletion or duplication of small sections of chromosomes can be a normal finding. There are also many chromosome level CNVs associated with known genetic syndromes.
De novo Mutation
Arising spontaneously; a de novo variant is not generally inherited from a parent. Once present in a family, a pathogenic de novo variant can be passed on to offspring in the inheritance pattern typical for the disorder.
When one copy of a pathogenic variant in a gene causes the development of symptoms/disease.
Offspring of affected individuals each have a 50% chance of inheriting the pathogenic variant. If inherited, the offspring will be affected by the same symptoms/disease.
The number of times a particular variant is seen in a population.
Major and minor allele frequencies refer to the general population and are expressed as a fraction or percentage. Variant allele frequency (VAF) refers to an individual’s genetic test result for a particular variant. VAF is more often used in reference to tumor testing in cancer.
All of the DNA for an individual, a population, or a species.
An individual’s genetic makeup at the DNA level; presence or absence of variants.
Loss of function in one copy of a gene pair, leaving one functional copy that produces some protein, but not enough to prevent the specific disease or genetic condition.
Inheriting two identical copies (alleles) of a gene, one from each parent.
Inheriting two identical alleles of a gene, one from each parent.
When the inheritance and expression of a gene depends on whether the gene was inherited from the father or mother.
A single phenotype (disorder or features) resulting from one or more variants in different genes.
The addition of a methyl group (CH3). Methylation of DNA does not change the gene sequence but may change or repress gene expression, and therefore the function of the gene. Methylated DNA is transmitted from parent to offspring and can depend on which parent passes it on (see Imprinting).
A change in the DNA (single nucleotide substitution) that alters the type of amino acid at that position in the gene. This change in amino acid may impact the function of the protein.
A change (variant) in the DNA of the mitochondria, which is passed from a mother to all of her offspring (matrilineal inheritance). Since each cell has many mitochondria, the frequency of the variant may differ in different tissues, resulting in variable phenotype among offspring. Mitochondrial DNA results from a blood sample may not be a true reflection of the frequency in other tissues.
A missing chromosome, when a pair is expected. For instance, a female with 45 chromosomes, including one instead of the expected two copies of X, has Turner syndrome.
Presence or mix of two or more populations of cells with different genotypes in one individual.
A type of inheritance pattern without a single genetic cause. The interaction of genes, even genes inherited from each parent, in combination with lifestyle or environmental factors may lead to the condition or phenotype.
A change in DNA sequence.
Note: The word mutation has now been replaced with variant, and usually includes further classification, such as pathogenic (disease-causing), likely-pathogenic, likely-benign, benign (not associated with disease), or variant of uncertain clinical significance.
A sequence variant that changes the original codon into a premature stop codon, resulting in (typically) a non-functional, shortened protein.
A genetic change associated with increased susceptibility or predisposition to a disease or disorder; also called a disease-causing variant.
Variants should meet multiple lines of evidence to be classified as pathogenic; refer to the American College of Medical Genetics and Genomics 2015 Guidelines for further information.
The extent to which a particular phenotype is expressed in individuals that carry a gene variant. The penetrance is 100% for variants which always lead to the characteristic phenotype. Reduced or incomplete penetrance is noted when multiple individuals may have the same gene change, even within the same family, but some have no sign or symptoms of the disorder (no recognized phenotype).
The study of genetic variants and their effect on how medications are processed within the body. This can also be referred to as pharmacogenetics.
The clinical features or symptoms observed as a result of genetic contribution (genotype) along with environmental influences.
A common variant or change in DNA which does not lead to disease or symptoms. New terminology refers to high-frequency genetic variants as benign variants.
Prior authorization (PA), which is sometimes called preauthorization, is a requirement from a patient’s insurance company that approval is granted by the insurer before some tests, treatments, or procedures are performed.
Refer to Insurance & Genetic Testing for more information.
The affected individual through whom a genetic study of a family starts; also known as the index case.
Two disease-causing (pathogenic) variants in a gene (usually one copy from each parent) that are required for disease development.
Parents who have one pathogenic variant (often referred to as carriers) are typically not affected with the condition; however, when parents who are carriers of pathogenic variants in the same gene have children, each child has a 25% chance of inheriting the disease.
Single Nucleotide Polymorphism (SNP)
A single base pair change or variant in DNA sequence frequently found in the general population.
Splice Site Mutation
A change or variant in the DNA sequence that occurs at the boundary of an exon and intron (splice site). Splice site variants can disrupt the translation of DNA to RNA, lead to skipping of an exon, the addition of intron(s) to the RNA, and may result in an abnormal or non-functional protein.
When a chromosome breaks and reattaches to a chromosome from a different pair.
Having an additional copy of a chromosome, resulting in three copies of a particular chromosome instead of the expected two.
Down syndrome is usually caused by trisomy 21, where there are three copies of chromosome 21.
Shortened protein that is often non-functional; usually the result of a nonsense or premature termination variant.
The differing presentation of symptoms or disease amongst individuals with identical genetic changes. This can be seen even within the same family.
A change in the DNA sequence of a person’s genome that occurs at random or is inherited.
Variants can be pathogenic (disease-causing), likely-pathogenic, benign (not associated with disease), likely-benign, or of uncertain clinical significance.
Variant of Uncertain Significance (VUS)
A genetic change or variant that is different from the typical gene sequence but for which there is insufficient information to know whether it is associated with disease formation or with normal genetic variation. Refer to the American College of Medical Genetics and Genomics’ 2015 Guidelines for further information.
An inheritance pattern associated with variants found on the X chromosome. Genes on the X chromosome are called X-linked.
Generally, males have only one X chromosome and are typically more likely to be affected by X-linked disease (or more severely affected) than females, who typically have two X chromosomes.