VARS2
Basic information
Region (hg38): 6:30914205-30926459
Previous symbols: [ "VARS2L", "VARSL" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
- 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 | 73 | 85 | ||||
missense | 236 | 20 | 270 | |||
nonsense | 15 | |||||
start loss | 0 | |||||
frameshift | 10 | |||||
splice donor/acceptor (+/-2bp) | 12 | 15 | ||||
Total | 14 | 33 | 247 | 93 | 8 |
Highest pathogenic variant AF is 0.000328212
GnomAD
Source:
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:
- 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