Table 1 |.

Glossary of human genetics terms

Domain	Term	Definition
Mode of inheritance	Autosomal dominant	A single copy of a gene variant on a non-sex chromosome is sufficient to cause disease
	Autosomal recessive	A variant on each gene copy is required to cause disease
	X-linked	Gene variants encoded on the X chromosome can exhibit dominant or recessive transmission
	Hemizygous	Presence of a single gene copy in diploid cells, such as the X chromosome in males
	Mosaicism	The presence of at least two cell populations with differing genotypes, resulting in a gene variant being present in only a subset of cells
	De novo variant	A gene variant in an individual that is absent from both parents, and arises due to new mutation of parental gametes or after fertilization
	Monogenic inheritance	A single gene is causative for a trait
	Polygenic inheritance	Many genes contribute to a trait
	Oligogenic inheritance	A few genes influence the trait
Variant types	Indel	An insertion or deletion of a sequence of 1–49 base pairs
	Aneuploidy	An abnormal number of chromosomes
	Structural variant	A broad class of variants encompassing ≥50 base pairs of sequence that includes deletions, duplications, inversions, insertions or transversions
	Copy number variant	An unbalanced structural variant (deletion, duplication or insertion) that alters the copy number of a gene or genes
Molecular consequences of genetic variants	Damaging	A general descriptive term indicating that a variant alters the expression level or function of a gene
	Loss-of-function	A variant that extinguishes the expression of one gene copy or abrogates its function
	Gain-of-function	A variant that enhances gene function, produces a new function or inappropriately increases gene expression
	Frameshift	Insertion or deletion of nucleotides that shifts the triplet amino acid code used for translation of mRNA to protein
	Missense	A variant that substitutes one amino acid for another in the protein sequence
	Synonymous	A variant that alters a nucleotide but does not alter the amino acid sequence of the encoded protein
	Splicing	A gene variant that alters canonical nucleotide signals to excise introns or exclude exons from mature mRNAs; splicing variants can abrogate existing splice signals or create new splice signals
Genotype–phenotype relationship	Variable expressivity	Variation in phenotype among individuals with the causal genetic variant
	Penetrance	The proportion of individuals who manifest the phenotype associated with a genetic variant