YARS2

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

Basic information

Region (hg38): 12:32727489-32755897

Links

ENSG00000139131 ∙ NCBI:51067 ∙ OMIM:610957 ∙ HGNC:24249 ∙ Uniprot:Q9Y2Z4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopathy, lactic acidosis, and sideroblastic anemia 2 (Definitive), mode of inheritance: AR
• myopathy, lactic acidosis, and sideroblastic anemia 2 (Strong), mode of inheritance: AR
• myopathy, lactic acidosis, and sideroblastic anemia (Supportive), mode of inheritance: AR
• myopathy, lactic acidosis, and sideroblastic anemia 2 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, lactic acidosis, and sideroblastic anemia 2	AR	Cardiovascular; Hematologic	Individuals may develop transfusion-dependent sideroblastic anemia in infancy; Surveillance for cardiovascular manifestations may allow early medical interventions	Cardiovascular; Hematologic; Musculoskeletal	20598274; 22504945; 24344687; 24430573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YARS2 gene.

• not provided (190 variants)
• Myopathy, lactic acidosis, and sideroblastic anemia 2 (48 variants)
• Hereditary Sideroblastic Anemia with Myopathy and Lactic Acidosis (26 variants)
• Inborn genetic diseases (19 variants)
• Myopathy, lactic acidosis, and sideroblastic anemia (18 variants)
• not specified (14 variants)
• Lethal Encephalopathy (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YARS2 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			2	42	1	45
missense	1	9	79	3		92
nonsense	4	1	1			6
start loss						0
frameshift	7	2	1			10
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)						0
splice region			2	3		5
non coding			6	22	8	36
Total	12	13	93	67	9

Highest pathogenic variant AF is 0.000230

Variants in YARS2

This is a list of pathogenic ClinVar variants found in the YARS2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-32730955-A-G			Likely benign (Jun 14, 2018)
12-32730998-C-T		not specified	Benign (Jan 30, 2024)
12-32731003-T-C			Likely benign (Oct 03, 2023)
12-32731007-C-T			Likely benign (Jun 29, 2021)
12-32731017-C-T		not specified	Likely benign (Dec 30, 2023)
12-32731018-G-A		Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 • DNM1L-related disorder	Pathogenic (Dec 01, 2023)
12-32731019-G-A		Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1	Likely pathogenic (Jan 01, 2015)
12-32731021-G-A		Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1	Likely pathogenic (Feb 19, 2021)
12-32731022-G-A		Mitochondrial disease	Likely pathogenic (Oct 08, 2021)
12-32731022-G-T			Uncertain significance (Oct 04, 2022)
12-32731025-C-A			Likely pathogenic (Apr 01, 2019)
12-32731033-T-C			Likely pathogenic (Apr 01, 2020)
12-32731038-T-C			Likely benign (Dec 09, 2023)
12-32731042-T-C		Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1	Likely pathogenic (May 28, 2019)
12-32731058-G-C			Uncertain significance (Jan 13, 2020)
12-32731061-G-A			Uncertain significance (Dec 27, 2022)
12-32731069-G-A		Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1	Likely pathogenic (Jun 23, 2014)
12-32731075-G-A			Uncertain significance (Jul 19, 2022)
12-32731076-T-C		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
12-32731084-C-T			Uncertain significance (Sep 10, 2023)
12-32731118-C-A		Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1	Pathogenic (Oct 15, 2010)
12-32731124-G-C			Uncertain significance (Dec 17, 2021)
12-32731127-A-G			Uncertain significance (Jan 02, 2024)
12-32731142-T-C			Likely benign (Sep 20, 2021)
12-32731143-G-A		not specified • DNM1L-related disorder	Benign/Likely benign (Jan 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YARS2	protein_coding	protein_coding	ENST00000324868	5	28413

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.00e-11	0.155	125327	1	420	125748	0.00168

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.264	247	259	0.954	0.0000130	3074
Missense in Polyphen		62	72.149	0.85934		874
Synonymous	-0.966	121	108	1.12	0.00000552	1013
Loss of Function	0.629	18	21.1	0.852	0.00000126	205

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0144	0.0144
Ashkenazi Jewish	0.00	0.00
East Asian	0.000333	0.000326
Finnish	0.00296	0.00296
European (Non-Finnish)	0.000618	0.000615
Middle Eastern	0.000333	0.000326
South Asian	0.000261	0.000261
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr- AMP and then transferred to the acceptor end of tRNA(Tyr). {ECO:0000269|PubMed:15779907, ECO:0000269|PubMed:17997975}.
• Disease: DISEASE: Myopathy with lactic acidosis and sideroblastic anemia 2 (MLASA2) [MIM:613561]: A rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest sideroblastic anemia, progressive lethargy, muscle weakness, and exercise intolerance associated with persistent lactic acidemia. {ECO:0000269|PubMed:20598274, ECO:0000269|PubMed:22504945}. 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;Tyrosine metabolism;tRNA charging;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.285

Intolerance Scores

• loftool: 0.846
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.109
• hipred: N
• hipred_score: 0.317
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Yars2

Gene ontology

• Biological process: translation;tRNA aminoacylation for protein translation;tRNA aminoacylation;mitochondrial tyrosyl-tRNA aminoacylation
• Cellular component: mitochondrion;mitochondrial matrix;cytosol;nuclear body
• Molecular function: tRNA binding;RNA binding;tyrosine-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;tyrosine binding