GeneBe

DARS2

aspartyl-tRNA synthetase 2, mitochondrial, the group of Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 1:173824653-173858808

Links

ENSG00000117593 ∙ NCBI:55157 ∙ OMIM:610956 ∙ HGNC:25538 ∙ Uniprot:Q6PI48 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (Strong), mode of inheritance: AR
  • leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (Definitive), mode of inheritance: AD
  • leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (Strong), mode of inheritance: AR
  • leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (Supportive), mode of inheritance: AR
  • leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (Strong), mode of inheritance: AR
  • mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevationARGeneralGenetic 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; Neurologic15326244; 17384640; 19592391; 21749991; 21815884; 22677571; 23065766; 23644316

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DARS2 gene.

  • not_provided (303 variants)
  • Leukoencephalopathy_with_brain_stem_and_spinal_cord_involvement-high_lactate_syndrome (159 variants)
  • Inborn_genetic_diseases (68 variants)
  • not_specified (20 variants)
  • DARS2-related_disorder (13 variants)
  • Dysmetria (2 variants)
  • Hypertensive_disorder (2 variants)
  • Abnormal_foot_morphology (2 variants)
  • Gout (2 variants)
  • CNS_demyelination (2 variants)
  • See_cases (2 variants)
  • Clubfoot (2 variants)
  • Difficulty_walking (2 variants)
  • Cerebral_cortical_atrophy (2 variants)
  • Impaired_vibration_sensation_in_the_lower_limbs (2 variants)
  • Spastic_ataxia (2 variants)
  • Mitochondrial_disease (2 variants)
  • Gait_ataxia (2 variants)
  • EMG:_axonal_abnormality (2 variants)
  • Sensorimotor_neuropathy (2 variants)
  • Gait_imbalance (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DARS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018122.5. 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
2
clinvar
1
clinvar
3
clinvar
47
clinvar
 53
missense
3
clinvar
24
clinvar
156
clinvar
11
clinvar
1
clinvar
 195
nonsense
5
clinvar
9
clinvar
1
clinvar
 15
start loss
1
 1
frameshift
12
clinvar
8
clinvar
 20
splice donor/acceptor (+/-2bp)
2
clinvar
9
clinvar
1
clinvar
 12
Total 24 52 161 58 1

Highest pathogenic variant AF is 0.0051621315

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DARS2protein_codingprotein_codingENST00000361951 1734044
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
9.79e-130.88812559301551257480.000616
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.192853480.8200.00001794203
Missense in Polyphen83117.090.708861328
Synonymous0.9621081210.8890.000005811251
Loss of Function1.972538.20.6550.00000210451

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006800.000680
Ashkenazi Jewish0.002180.00218
East Asian0.0002720.000272
Finnish0.001710.00171
European (Non-Finnish)0.0005030.000501
Middle Eastern0.0002720.000272
South Asian0.0002290.000229
Other0.001310.00130

dbNSFP

Source: dbNSFP

Disease
DISEASE: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) [MIM:611105]: Autosomal recessive disease and is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. {ECO:0000269|PubMed:17384640}. 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;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

pRec
0.172

Intolerance Scores

loftool
0.406
rvis_EVS
0.2
rvis_percentile_EVS
67.19

Haploinsufficiency Scores

pHI
0.365
hipred
N
hipred_score
0.204
ghis
0.583

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.996

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Dars2
Phenotype
mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process
tRNA aminoacylation for protein translation;tRNA aminoacylation;mitochondrial asparaginyl-tRNA aminoacylation
Cellular component
nucleus;mitochondrion;mitochondrial matrix
Molecular function
tRNA binding;aspartate-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;aspartate-tRNA(Asn) ligase activity