PARS2

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

Basic information

Region (hg38): 1:54756898-54764523

Links

ENSG00000162396 ∙ NCBI:25973 ∙ OMIM:612036 ∙ HGNC:30563 ∙ Uniprot:Q7L3T8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 75 (Moderate), mode of inheritance: AR
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 75 (Strong), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 75	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; Cardiovascular; Gastrointestinal; Neurologic; Renal	25629079; 27290639; 28077841; 29410512; 29915213

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PARS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PARS2 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				40	1	41
missense			74	2	3	79
nonsense		3	1			4
start loss						0
frameshift			1			1
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				7	5	12
Total	0	3	76	50	9

Variants in PARS2

This is a list of pathogenic ClinVar variants found in the PARS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-54757495-A-C			Likely benign (Jul 07, 2018)
1-54757517-C-T			Benign (Jun 26, 2018)
1-54757524-G-A			Likely benign (Jul 07, 2018)
1-54757589-T-C			Likely benign (Jun 26, 2018)
1-54757760-A-G			Likely benign (Aug 17, 2023)
1-54757792-A-G			Uncertain significance (Jun 17, 2022)
1-54757798-C-T		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
1-54757822-A-C		Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
1-54757828-G-A			Uncertain significance (Dec 02, 2021)
1-54757851-G-C		not specified	Benign (Nov 27, 2023)
1-54757857-G-A			Likely benign (Aug 01, 2022)
1-54757863-C-T			Benign/Likely benign (Nov 01, 2023)
1-54757907-C-T		Inborn genetic diseases	Uncertain significance (Dec 06, 2023)
1-54757908-G-A		not specified	Likely benign (Apr 21, 2016)
1-54757920-G-T			Likely benign (Aug 10, 2023)
1-54757938-C-G			Likely benign (Nov 28, 2022)
1-54757985-G-A			Likely benign (Oct 11, 2022)
1-54758000-C-T			Uncertain significance (Apr 18, 2022)
1-54758004-G-A		PARS2-related disorder	Benign/Likely benign (Jan 01, 2024)
1-54758005-G-A			Uncertain significance (Aug 17, 2022)
1-54758008-G-A		PARS2-related disorder	Benign/Likely benign (Jan 22, 2024)
1-54758021-T-C			Uncertain significance (Aug 01, 2024)
1-54758031-A-AG		Developmental and epileptic encephalopathy, 75	Pathogenic (Jan 01, 2015)
1-54758033-G-A		Developmental and epileptic encephalopathy, 75	Uncertain significance (Jan 01, 2019)
1-54758033-G-C			Uncertain significance (Dec 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PARS2	protein_coding	protein_coding	ENST00000371279	1	7617

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00412	0.964	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.288	266	280	0.952	0.0000164	3075
Missense in Polyphen		96	101.09	0.9496		1128
Synonymous	0.780	106	117	0.908	0.00000655	1006
Loss of Function	1.88	6	13.4	0.447	7.45e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000365	0.000362
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.000326	0.000326
South Asian	0.0000653	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• 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: 0.149

Intolerance Scores

• loftool: 0.333
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.71

Haploinsufficiency Scores

• pHI: 0.148
• hipred: Y
• hipred_score: 0.547
• ghis: 0.545

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pars2

Gene ontology

• Biological process: prolyl-tRNA aminoacylation
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: proline-tRNA ligase activity;ATP binding