EARS2
Basic information
Region (hg38): 16:23520754-23557731
Links
Phenotypes
GenCC
Source:
- leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome (Strong), mode of inheritance: AR
- Leigh syndrome (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Combined oxidative phosphorylation deficiency 12 | 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 | 22492562; 23008233 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (6 variants)
- Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome (6 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EARS2 gene is commonly pathogenic or not.
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.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 44 | 55 | ||||
missense | 11 | 119 | 138 | |||
nonsense | 9 | |||||
start loss | 1 | |||||
frameshift | 7 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
splice region | 3 | 3 | 6 | |||
non coding | 27 | 26 | 23 | 76 | ||
Total | 12 | 18 | 153 | 73 | 32 |
Highest pathogenic variant AF is 0.0000132
Variants in EARS2
This is a list of pathogenic ClinVar variants found in the EARS2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
16-23522062-C-T | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 13, 2018) | ||
16-23522077-A-G | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 12, 2018) | ||
16-23522178-T-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 13, 2018) | ||
16-23522215-A-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 13, 2018) | ||
16-23522266-G-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Likely benign (Jan 12, 2018) | ||
16-23522467-T-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 12, 2018) | ||
16-23522468-G-GT | Combined oxidative phosphorylation deficiency | Uncertain significance (Jun 14, 2016) | ||
16-23522469-T-G | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 13, 2018) | ||
16-23522562-A-G | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 13, 2018) | ||
16-23522563-C-T | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 12, 2018) | ||
16-23522651-C-T | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 13, 2018) | ||
16-23522724-G-A | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 12, 2018) | ||
16-23522777-G-A | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 13, 2018) | ||
16-23522873-T-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 13, 2018) | ||
16-23522928-G-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 13, 2018) | ||
16-23522936-G-T | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 12, 2018) | ||
16-23522963-T-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 12, 2018) | ||
16-23522983-G-A | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 13, 2018) | ||
16-23523009-A-G | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 13, 2018) | ||
16-23523044-T-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Likely benign (Jan 13, 2018) | ||
16-23523138-G-A | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 13, 2018) | ||
16-23523233-C-T | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 12, 2018) | ||
16-23523272-T-C | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Benign (Jan 12, 2018) | ||
16-23523289-A-G | Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome | Uncertain significance (Jan 13, 2018) | ||
16-23523322-CT-C | Combined oxidative phosphorylation deficiency | Uncertain significance (Jun 14, 2016) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
EARS2 | protein_coding | protein_coding | ENST00000449606 | 9 | 35718 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.12e-8 | 0.784 | 124756 | 0 | 60 | 124816 | 0.000240 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.108 | 303 | 308 | 0.983 | 0.0000184 | 3353 |
Missense in Polyphen | 105 | 122.03 | 0.86048 | 1331 | ||
Synonymous | -0.451 | 132 | 126 | 1.05 | 0.00000698 | 1085 |
Loss of Function | 1.48 | 16 | 23.8 | 0.672 | 0.00000117 | 256 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000427 | 0.000426 |
Ashkenazi Jewish | 0.0000994 | 0.0000993 |
East Asian | 0.000725 | 0.000723 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000195 | 0.000194 |
Middle Eastern | 0.000725 | 0.000723 |
South Asian | 0.000362 | 0.000360 |
Other | 0.000333 | 0.000330 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu). {ECO:0000250}.;
- Disease
- DISEASE: Combined oxidative phosphorylation deficiency 12 (COXPD12) [MIM:614924]: An autosomal recessive, mitochondrial, neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability. {ECO:0000269|PubMed:22492562, ECO:0000269|PubMed:23008233, ECO:0000269|PubMed:26741492}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Porphyrin and chlorophyll metabolism - Homo sapiens (human);2-Hydroxyglutric Aciduria (D And L Form);Homocarnosinosis;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Glutamate Metabolism;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
- 0.386
Intolerance Scores
- loftool
- 0.674
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 57.31
Haploinsufficiency Scores
- pHI
- 0.0899
- hipred
- N
- hipred_score
- 0.204
- ghis
- 0.507
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.979
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ears2
- Phenotype
Gene ontology
- Biological process
- glutamyl-tRNA aminoacylation;tRNA aminoacylation for mitochondrial protein translation
- Cellular component
- mitochondrion;mitochondrial matrix
- Molecular function
- tRNA binding;glutamate-tRNA ligase activity;ATP binding;zinc ion binding;glutamate-tRNA(Gln) ligase activity