Genetics · BEGINNER LESSON
Genetic variant
A genetic variant is a change in DNA sequence or DNA structure compared with another reference sequence. Variants can be inherited, acquired in some cells, or detected as single-base changes, small insertions/deletions, or larger rearrangements.
What it is and what is measured
A genetic variant is a difference in DNA, the molecule that stores hereditary information in living organisms. In practice, scientists measure what kind of DNA change is present and where it is found in the genome. Common measured forms include single-nucleotide variants (SNVs), insertion-deletion variants (indels), copy number variants (CNVs), and structural variants (SVs). A variant can also be described by variant allele frequency (VAF), which estimates how often the variant is seen in sequencing reads at a specific DNA position. [0,2]
[1] Table 1. Key terms and concepts. [3] Patient Safety And Education
Main kinds of variants
An SNV is a change where one nucleotide is replaced by another. An indel is a small insertion or deletion of fewer than 50 base pairs, where a base pair is one paired DNA building block. A CNV changes the number of copies of a DNA region by duplication or deletion. An SV is a larger rearrangement of part of the genome, larger than 50 base pairs. Some SNVs in coding regions do not change the amino acid made by a gene, while others do. [0,2]
[1] Table 1. Key terms and concepts. [3] Patient Safety And Education
How variants arise and where they matter
Variants may be germline, meaning they are present in germ cells and can be passed to all cells of the organism and to offspring, or somatic, meaning they are acquired and present only in a subset of cells. Whole-genome sequencing (WGS), which reads DNA across the genome, can identify SNVs, indels, CNVs, and variants that affect splicing patterns or non-coding RNAs. Genome-wide association studies (GWAS), which test many variants across the genome, often find common SNPs as markers for underlying functional variants. [0,1]
[1] Table 1. Key terms and concepts. [2] Role of common host genome variants in Childhood Acute ...
Limits and interpretation
Finding a variant does not automatically show that it causes a trait or disease. Studies may face multiple-testing problems, limited power for rare variants, and the need for replication in diverse populations. Some variants are classified with evidence frameworks such as the American College of Medical Genetics criteria, which range from pathogenic to benign. Public resources such as ClinVar collect reported links between human variants and phenotypes. [0,1]
[1] Table 1. Key terms and concepts. [2] Role of common host genome variants in Childhood Acute ...
SEE THE IDEA
From DNA change to interpretation
A difference from a reference sequence is observed in DNA.
The change is described as SNV, indel, CNV, or SV.
It may be germline in all cells or somatic in only some cells.
Sequencing, VAF, GWAS, and classification rules help judge significance.
Each step narrows what kind of variant is present and how confidently it can be interpreted.
A variant is first identified as a DNA change, then described, located, and interpreted with evidence.
TRY IT YOURSELF
Test your understanding
Choose an answer, then check the explanation.
PUT IT TOGETHER
Match each concept to its meaning
Drag a label onto its description, or select a label and then select a description. This also works with a keyboard.
4 pairs to match
Sources and further reading
This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.