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

ENSG00000137411NCBI:57176OMIM:612802HGNC:21642Uniprot:Q5ST30AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Combined oxidative phosphorylation deficiency 20ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingBiochemical; Neurologic24827421; 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.

EffectPLPVUSLBBSum
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

GeneTypeBio TypeTranscript Coding Exons Length
VARS2protein_codingprotein_codingENST00000541562 3018218
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
5.83e-171.0012555901891257480.000752
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.394516180.7290.00003556901
Missense in Polyphen145226.050.641442611
Synonymous2.022132540.8390.00001462277
Loss of Function3.733973.60.5300.00000442701

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001680.00166
Ashkenazi Jewish0.00009920.0000992
East Asian0.0003860.000381
Finnish0.0009260.000924
European (Non-Finnish)0.0006440.000615
Middle Eastern0.0003860.000381
South Asian0.001410.00141
Other0.0005170.000489

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

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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