Glossary

Autosomal recessive: genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
[Source – NCI Dictionary of Genetics Terms]

Benign (variant): an alteration in a gene distinct from the normal, wild-type allele that does.
[Source – Illustrated Glossary]

Carrier frequency: the proportion of individuals in a population who have a single copy of a specific recessive gene mutation; also sometimes applied to the prevalence of mutations in dominantly acting genes such as BRCA1 and BRCA2. Also called carrier rate.
[Source – NCI Dictionary of Genetics Terms]

Carrier: an individual who has a recessive, disease-causing variant at a particular location on one chromosome of a pair and a typically functioning allele at that location on the other chromosome.
[Source – CSER Consortium Practitioner Education Working Group]

Clinical sensitivity: the frequency with which a test yields a true positive result among individuals who actually have the disease or the gene mutation in question. A test with high sensitivity has a low false-negative rate and thus does a good job of correctly identifying affected individuals.
[Source – NCI Dictionary of Genetics Terms]

De novo (variant): an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents, or a mutation that arises in the fertilized egg itself during early embryogenesis. Also called a new mutation.
[Source – NCI Dictionary of Genetics Terms]

Exome: the exome is the small subset (1-2%) of an individual's entire genetic sequence, or genome, that directly instructs the building of a particular protein. Although a small fraction of the genome, the exome includes the sequence of approximately ~22,000 genes.
[Source – CSER Consortium Practitioner Education Working Group]

False negative: a test result which indicates that an individual is unaffected and/or does not have a particular gene mutation (variant) when he or she is actually affected and/or does have a gene mutation (variant); i.e., a negative test result in an affected individual.
[Source – Illustrated Glossary]

False positive: a test result which indicates that an individual is affected and/or has a certain gene mutation (variant) when he or she is actually unaffected and/or does not have the mutation (variant); i.e., a positive test result in a truly unaffected individual.
[Source – Illustrated Glossary]

Genetic variant: a change in the DNA sequence as compared to a reference sequence that may or may not have an impact on protein function or disease state. Terms such as mutation and polymorphism have been largely replaced by 'variant' to simplify terminology.
[Source – CSER Consortium Practitioner Education Working Group]

Genome: the entire set of genetic instructions found in a cell. In humans, the genome consists of 23 pairs of chromosomes, found in the nucleus, as well as a small chromosome found in the cells' mitochondria. Each set of 23 chromosomes contains approximately 3.1 billion bases of DNA sequence.
[Source – Talking Glossary of Genetic Terms]

Genome-wide association studies: a genome-wide association study (GWAS) is an approach used in genetics research to associate specific genetic variations with particular diseases. The method involves scanning the genomes from many different people and looking for genetic markers that can be used to predict the presence of a disease.
[Source – Talking Glossary of Genetic Terms]

Likely pathogenic variant: a DNA change that is most likely causing a deleterious effect on an encoded protein product that accounts for the observed symptoms.
[Source – CSER Consortium Practitioner Education Working Group]

Medically actionable: used to alter the treatment or surveillance of a patient.
[Source – CSER Consortium Practitioner Education Working Group]

Next generation sequencing: a high-throughput method used to determine a portion of the nucleotide sequence of an individual’s genome. This technique utilizes DNA sequencing technologies that are capable of processing multiple DNA sequences in parallel. Also called massively parallel sequencing and NGS.
[Source – NCI Dictionary of Genetics Terms]

Novel variant: a newly discovered, distinct genetic alteration; NOT the same as new or de novo variant (or mutation). Also called novel mutation.
[Source – NCI Dictionary of Genetics Terms]

Pathogenic: a genetic alteration that increases an individual’s susceptibility or predisposition to a certain disease or disorder. When such a variant (or mutation) is inherited, development of symptoms is more likely, but not certain. Also called deleterious mutation, disease-causing mutation, predisposing mutation, and susceptibility gene.
[Source – NCI Dictionary of Genetics Terms]

Penetrance: a characteristic of a genotype; it refers to the likelihood that a clinical condition will occur when a particular genotype is present.
[Source – NCI Dictionary of Genetics Terms]

Pharmacogenomics: a branch of pharmacology concerned with using DNA and amino acid sequence data to inform drug development and testing. An important application of pharmacogenomics is correlating individual genetic variation with drug responses.
[Source – Talking Glossary of Genetic Terms]

Phenotype: the observable characteristics in an individual resulting from the expression of genes; the clinical presentation of an individual with a particular genotype.
[Source – NCI Dictionary of Genetics Terms]

Polymorphism: a common mutation. “Common” is typically defined as an allele frequency of at least 1%. All genes occur in pairs, except when x and y chromosomes are paired in males; thus a polymorphism with an allele frequency of 1% would be found in about 2% of the population, with most carriers having one copy of the polymorphism and one copy of the normal allele.
[Source – NCI Dictionary of Genetics Terms]

Primary result: alterations in a gene or genes that are relevant to the diagnostic indication for which the test was ordered.
[Source – CSER Consortium Practitioner Education Working Group]

Reference sequence: the 'standard' sequence of DNA for a particular organism that is used to compare new sequence data against for alignment and identification of variation.
[Source – CSER Consortium Practitioner Education Working Group]

Repeat expansion: Some areas within the human genome contain small repetitive sequences of DNA (i.e. CAG). The number of repeats at a particular genomic location is typically stable. However, an increase in repeat number has been associated with several human diseases such as Huntington Disease and Fragile X syndrome.
[Source – CSER Consortium Practitioner Education Working Group]

Sanger sequencing: a low-throughput method used to determine a portion of the nucleotide sequence of an individual’s genome. This technique uses polymerase chain reaction (PCR) amplification of genetic regions of interest followed by sequencing of PCR products.
[Source – NCI Dictionary of Genetics Terms]

Secondary result: refers to genomic test results that do not pertain to the primary diagnostic question or reason for testing. Also referred to as an incidental finding.
[Source – CSER Consortium Practitioner Education Working Group]

Single nucleotide polymorphism: DNA sequence variation that occurs when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered; usually present in at least 1% of the population. Also called SNP.
[Source – NCI Dictionary of Genetics Terms]

Singleton: typically used to refer to the sequencing of one individual rather than a family unit.
[Source – CSER Consortium Practitioner Education Working Group]

Toxicity: the dosage at which a drug causes adverse effects within the body.
[Source – CSER Consortium Practitioner Education Working Group]

Trio: typically refers to the sequencing and analysis of an affected individual as well has his or her mother and father.
[Source – CSER Consortium Practitioner Education Working Group]

Variant calling: the process of comparing a DNA sequence of interest to a reference.
[Source – CSER Consortium Practitioner Education Working Group]

Variant of uncertain significance: A variant of uncertain significance is a change in the DNA sequence whose association with disease is unknown. Also called a variant of unknown significance, unclassified variant, or sometimes simply a VUS.
[Source – CSER Consortium Practitioner Education Working Group]

X-linked recessive: a mode of inheritance in which a mutation (variant) in a gene on the X chromosome causes the phenotype (symptoms) to be expressed in males who are hemizygous for the gene mutation (i.e., they have only one X chromosome) and in females who are homozygous for the gene mutation (i.e., they have a copy of the gene mutation on each of their two X chromosomes). Carrier females who have only one copy of the mutation do not usually express the phenotype, although differences in X-chromosome inactivation can lead to varying degrees of clinical expression in carrier females.
[Source – Illustrated Glossary]