See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

Includes the hypomorphic variant c.37T>G (p.Trp13Gly), which is only disease causing when present in trans with loss-of-function pathogenic variants [Ilinca et al 2022, Skorvanek et al 2022]. Of note, the p.Trp13Gly variant is typically not detected by standard filtering criteria of exome sequencing. Therefore, if another pathogenic WARS2 variant is detected in the heterozygous state, using additional and/or modified filters to specifically confirm/exclude the presence of the p.Trp13Gly hypomorphic variant in trans is recommended (see Molecular Genetics).

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

One individual with a 36-kb deletion including exon 2 of WARS2 had a severe fatal neonatal form of disease that might also be explained by the presence of another variant (p.Val349Leu) with a more significant deleterious effect and possibly other modifiers. Additionally, two sibs with levodopa-responsive parkinsonism had the p.Trp13Gly variant in compound heterozygosity with an exon 2 deletion. Deletion of exon 2 is predicted to result in an in-frame deletion of 86 amino acids (p.Lys31_Q116del), consistent with a loss-of-function effect [Wortmann et al 2017, Skorvanek et al 2022].