VARS2

valyl-tRNA synthetase 2, mitochondrial, the group of Aminoacyl tRNA synthetases, Class I

Basic information

Region (hg38): 6:30914205-30926459

Previous symbols: [ "VARS2L", "VARSL" ]

Links

ENSG00000137411

∙ NCBI:57176 ∙ OMIM:612802 ∙ HGNC:21642 ∙ Uniprot:Q5ST30 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

combined oxidative phosphorylation defect type 20 (Moderate), mode of inheritance: AR
combined oxidative phosphorylation defect type 20 (Strong), mode of inheritance: AR
mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 20	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	24827421; 25058219; 31064326

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VARS2 gene.

not_provided (379 variants)
Inborn_genetic_diseases (138 variants)
Combined_oxidative_phosphorylation_defect_type_20 (55 variants)
not_specified (33 variants)
VARS2-related_disorder (21 variants)
See_cases (2 variants)
Hepatoencephalopathy_due_to_combined_oxidative_phosphorylation_defect_type_1 (1 variants)
Mitochondrial_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VARS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020442.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	73 clinvar	6 clinvar	85
missense	6 clinvar	6 clinvar	236 clinvar	20 clinvar	2 clinvar	270
nonsense	6 clinvar	7 clinvar	2 clinvar			15
start loss						0
frameshift	1 clinvar	8 clinvar	1 clinvar			10
splice donor/acceptor (+/-2bp)	1 clinvar	12 clinvar	2 clinvar			15
Total	14	33	247	93	8

Highest pathogenic variant AF is 0.000328212

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VARS2	protein_coding	protein_coding	ENST00000541562	30	18218

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.83e-17	1.00	125559	0	189	125748	0.000752

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.39	451	618	0.729	0.0000355	6901
Missense in Polyphen		145	226.05	0.64144		2611
Synonymous	2.02	213	254	0.839	0.0000146	2277
Loss of Function	3.73	39	73.6	0.530	0.00000442	701

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00168	0.00166
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000386	0.000381
Finnish	0.000926	0.000924
European (Non-Finnish)	0.000644	0.000615
Middle Eastern	0.000386	0.000381
South Asian	0.00141	0.00141
Other	0.000517	0.000489

dbNSFP

Source: dbNSFP

Disease: DISEASE: Combined oxidative phosphorylation deficiency 20 (COXPD20) [MIM:615917]: A disorder due to mitochondrial respiratory chain complex defects. Clinical features are variable and include muscle weakness with hypotonia, central neurological disease with progressive external ophthalmoplegia, ptosis and ataxia, delayed psychomotor development, cardiomyopathy, abnormal liver function, facial dysmorphism, microcephaly and epilepsy. {ECO:0000269|PubMed:24827421, ECO:0000269|PubMed:25058219}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);tRNA Aminoacylation;Translation;Metabolism of proteins;tRNA charging;Valine, leucine and isoleucine degradation;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

pRec: 0.0913

Intolerance Scores

loftool: 0.993
rvis_EVS: 2.34
rvis_percentile_EVS: 98.4

Haploinsufficiency Scores

pHI: 0.0270
hipred: Y
hipred_score: 0.520
ghis: 0.408

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.429

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Vars2
Phenotype

Gene ontology

Biological process: valyl-tRNA aminoacylation;aminoacyl-tRNA metabolism involved in translational fidelity
Cellular component: mitochondrion;cytosol
Molecular function: aminoacyl-tRNA editing activity;valine-tRNA ligase activity;ATP binding