Variant

De Novo Variant

A genetic alteration that is present for the first time in one family member as a result of a variant in a germ cell (egg or sperm) of one of the parents, or a variant that arises in the fertilized egg itself during early embryogenesis. Also called de novo variant, and new variant.²

Deletion

Deletion is a type of variant involving the loss of genetic material. It can be small, involving a single missing DNA base pair, or large, involving a piece of a chromosome.⁴
Example: Original DNA Sequence: the gray cat ran down the hall; Deletion Sequence: the gray ___ ran down the hall
Deletion Illustration

Duplication

Frameshift

A frameshift variant is a type of variant involving the insertion or deletion of a nucleotide in which the number of deleted base pairs is not divisible by three. "Divisible by three" is important because the cell reads a gene in groups of three bases. Each group of three bases corresponds to one of 20 different amino acids used to build a protein. If a variant disrupts this reading frame, then the entire DNA sequence following the variant will be read incorrectly.⁴
Example: Original DNA Sequence: the gray cat ran down the hall; Frameshift insertion: thh egra yca tra ndow nth ehal l; Frameshift deletion: the rayc atr and ownt heh all
Frameshift Illustration

Insertion

Insertion is a type of variant involving the addition of genetic material. An insertion variant can be small, involving a single extra DNA base pair, or large, involving a piece of a chromosome.⁴
Example: Original DNA Sequence: the gray cat ran down the hall; Insertion Sequence: the gray red cat ran down the hall
Insertion Illustration

Large Genomic Rearrangements

Large genomic rearrangements are large deletions or insertions of DNA (i.e. an exon deleted) as well as structural changes such as translocations or inversions.¹³ 
Example: Original DNA Sequence: the gray cat ran down the hall; Large Genomic Rearrangement Sequence: the
Large genomic rearrangements make up approximately 12-18% of variants found in BRCA1.¹³

Microsatellite Instability (MSI)

A characteristic of cells that contain an abnormality in DNA mismatch repair (see microsatellite).³
Clinical Example: The presence of MSI in colorectal tumor tissue may be used as a marker for germline mutations in one of the DNA mismatch repair genes associated with Lynch Syndrome. MSI can also occur sporadically, and in these cases is related to gene hypermethylation.³

Missense

A characteristic of cells that contain an abnormality in DNA mismatch repair (see microsatellite).³
Example: Original DNA Sequence: the gray cat ran down the hall; Missense Sequence: the grey cat ran down the hall
Missense Illustration

Nonsense

A nonsense variant is the substitution of a single base pair that leads to the appearance of a stop codon where previously there was a codon specifying an amino acid. The presence of this premature stop codon results in the production of a shortened, and likely nonfunctional, protein.⁴
Example: Original DNA Sequence: the gray cat ran down the hall; Nonsense Sequence: the gray
Nonsense Illustration

Point Variant

A genetic alteration caused by the substitution of a single nucleotide for another nucleotide. Also called point mutation.² 

Polymorphism

A variant with a frequency in the general population of greater than 1%.⁸
Example: Many variants associated with drug metabolism (pharmacogenomics) are polymorphisms.

Single Nucleotide Polymorphism (also called Single Nucleotide Variant)

Single nucleotide polymorphisms (SNPs) are a type of polymorphism involving variation of a single base pair. Scientists are studying how single nucleotide polymorphisms, or SNPs (pronounced "snips"), in the human genome correlate with disease, drug response, and other phenotypes.⁴
SNP Illustration

Single Nucleotide Variant (also called Single Nucleotide Polymorphism)

A DNA sequence variation that occurs when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered. Single nucleotide variants may be rare or common in a population. Sometimes single nucleotide variants are referred to as single nucleotide polymorphisms if they are present in at least 1% of the population. Also called SNV.³

Substitution

A substitution is a type of variant where one base pair is replaced by a different base pair. The term also refers to the replacement of one amino acid in a protein with a different amino acid.⁴
Substitution Illustration