RNASEH2A

ribonuclease H2 subunit A

Basic information

Region (hg38): 19:12806584-12813640

Links

ENSG00000104889 ∙ NCBI:10535 ∙ OMIM:606034 ∙ HGNC:18518 ∙ Uniprot:O75792 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Aicardi-Goutieres syndrome 4 (Definitive), mode of inheritance: AR
• Aicardi-Goutieres syndrome 4 (Strong), mode of inheritance: AR
• Aicardi-Goutieres syndrome 4 (Strong), mode of inheritance: AR
• Aicardi-Goutieres syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aicardi-Goutieres syndrome 4	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	Cardiovascular; Gastrointestinal; Dermatologic; Cardiovascular; Hematologic; Neurologic	16845400; 17846997; 20301648

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASEH2A gene.

• Aicardi-Goutieres syndrome 4 (13 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASEH2A 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		1		118	4	123
missense	1	6	162	4	2	175
nonsense	5	1	1			7
start loss			1			1
frameshift	7	2	4			13
inframe indel			3			3
splice donor/acceptor (+/-2bp)		8				8
splice region			8	19	2	29
non coding			13	81	15	109
Total	13	18	184	203	21

Highest pathogenic variant AF is 0.0000526

Variants in RNASEH2A

This is a list of pathogenic ClinVar variants found in the RNASEH2A region.

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

Position	Type	Phenotype	Significance	ClinVar
19-12806605-G-A		Aicardi-Goutieres syndrome 4	Uncertain significance (Jan 12, 2018)
19-12806625-C-T		Aicardi Goutieres syndrome • Aicardi-Goutieres syndrome 4	Uncertain significance (Jan 13, 2018)
19-12806649-A-G		Aicardi Goutieres syndrome	Uncertain significance (Jun 14, 2016)
19-12806658-T-C		Aicardi-Goutieres syndrome 4 • not specified	Benign (Jan 13, 2018)
19-12806674-A-G		Aicardi-Goutieres syndrome 4	Uncertain significance (Jun 15, 2022)
19-12806677-G-T		Aicardi-Goutieres syndrome 4	Uncertain significance (Aug 02, 2022)
19-12806678-A-G		Aicardi-Goutieres syndrome 4	Uncertain significance (Aug 24, 2021)
19-12806681-T-C		Aicardi-Goutieres syndrome 4	Uncertain significance (Aug 02, 2022)
19-12806686-G-T		Aicardi-Goutieres syndrome 4	Pathogenic (Apr 17, 2023)
19-12806688-G-A		Aicardi-Goutieres syndrome 4	Likely benign (Jun 15, 2022)
19-12806689-C-T		Aicardi-Goutieres syndrome 4	Likely benign (Jul 30, 2020)
19-12806691-G-A		Aicardi-Goutieres syndrome 4	Likely benign (Jul 16, 2023)
19-12806694-G-A		Aicardi-Goutieres syndrome 4	Likely benign (Aug 10, 2022)
19-12806698-G-A		Aicardi-Goutieres syndrome 4	Uncertain significance (Aug 23, 2022)
19-12806702-A-G		Aicardi-Goutieres syndrome 4	Uncertain significance (Aug 31, 2021)
19-12806705-C-T		Aicardi-Goutieres syndrome 4	Uncertain significance (Mar 19, 2022)
19-12806706-A-G		not specified • Aicardi-Goutieres syndrome 4	Benign (Feb 01, 2024)
19-12806707-G-A		Aicardi-Goutieres syndrome 4	Uncertain significance (Jun 20, 2022)
19-12806709-C-T		Aicardi-Goutieres syndrome 4	Conflicting classifications of pathogenicity (Jan 22, 2024)
19-12806711-G-T		Aicardi-Goutieres syndrome 4	Uncertain significance (Mar 23, 2022)
19-12806717-G-A		Aicardi-Goutieres syndrome 4	Uncertain significance (Jul 31, 2019)
19-12806718-C-A		Aicardi-Goutieres syndrome 4	Likely benign (May 19, 2023)
19-12806719-C-T		Aicardi-Goutieres syndrome 4 • RNASEH2A-related disorder	Likely benign (Jan 25, 2024)
19-12806727-G-T		Aicardi-Goutieres syndrome 4	Likely benign (Jan 16, 2024)
19-12806728-C-G		Aicardi-Goutieres syndrome 4	Uncertain significance (Apr 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASEH2A	protein_coding	protein_coding	ENST00000221486	8	7059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00418	0.965	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.193	171	178	0.959	0.0000116	1920
Missense in Polyphen		60	74.049	0.81027		831
Synonymous	-0.591	84	77.4	1.09	0.00000527	601
Loss of Function	1.88	6	13.5	0.446	5.92e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00166	0.00166
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000508	0.000508
European (Non-Finnish)	0.0000527	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging- strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:21177858}.
• Disease: DISEASE: Aicardi-Goutieres syndrome 4 (AGS4) [MIM:610333]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:17846997, ECO:0000269|PubMed:20131292}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: DNA replication - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.484

Intolerance Scores

• loftool: 0.254
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

• pHI: 0.815
• hipred: Y
• hipred_score: 0.723
• ghis: 0.654

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnaseh2a

Gene ontology

• Biological process: DNA replication;mismatch repair;RNA catabolic process;DNA replication, removal of RNA primer;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: nucleoplasm;cytosol;ribonuclease H2 complex
• Molecular function: RNA binding;RNA-DNA hybrid ribonuclease activity;ribonuclease activity;metal ion binding