RNASEH2B

ribonuclease H2 subunit B

Basic information

Region (hg38): 13:50909746-51024120

Previous symbols: [ "DLEU8", "AGS2" ]

Links

ENSG00000136104 ∙ NCBI:79621 ∙ OMIM:610326 ∙ HGNC:25671 ∙ Uniprot:Q5TBB1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Aicardi-Goutieres syndrome 2 (Definitive), mode of inheritance: AR
• Aicardi-Goutieres syndrome 2 (Strong), mode of inheritance: AR
• Aicardi-Goutieres syndrome (Supportive), mode of inheritance: AD
• Aicardi-Goutieres syndrome 2 (Definitive), mode of inheritance: AR
• prostate cancer (Limited), mode of inheritance: AD
• Aicardi-Goutieres syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aicardi-Goutieres syndrome 2	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; Hematologic; Neurologic	9706629; 16845400; 20301648; 25243380

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASEH2B gene.

• Aicardi-Goutieres syndrome 2 (361 variants)
• not provided (50 variants)
• not specified (15 variants)
• Inborn genetic diseases (12 variants)
• Aicardi Goutieres syndrome (5 variants)
• RNASEH2B-related condition (2 variants)
• Autism spectrum disorder (2 variants)
• Cerebral palsy (1 variants)
• Abnormality of the nervous system (1 variants)
• Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASEH2B 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	58	1	61
missense	1	6	129	3	1	140
nonsense	5	1	1			7
start loss	1					1
frameshift	8	1	7	1		17
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	10				12
splice region		2	14	18	2	36
non coding		2	20	74	10	106
Total	17	20	162	136	12

Highest pathogenic variant AF is 0.0000197

Variants in RNASEH2B

This is a list of pathogenic ClinVar variants found in the RNASEH2B region.

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

Position	Type	Phenotype	Significance	ClinVar
13-50909764-C-G		Aicardi Goutieres syndrome	Uncertain significance (Jun 14, 2016)
13-50909783-C-T		Aicardi-Goutieres syndrome 2	Uncertain significance (Jan 13, 2018)
13-50909784-A-G		Aicardi-Goutieres syndrome 2	Uncertain significance (Mar 02, 2018)
13-50909849-C-A		Aicardi-Goutieres syndrome 2	Uncertain significance (Jan 13, 2018)
13-50909867-G-C		Aicardi-Goutieres syndrome 2	Benign/Likely benign (Apr 29, 2021)
13-50909896-G-A		Aicardi-Goutieres syndrome 2	Uncertain significance (Jan 13, 2018)
13-50909932-G-A		Aicardi-Goutieres syndrome 2	Uncertain significance (Jan 12, 2018)
13-50909960-C-G		Aicardi-Goutieres syndrome 2	Likely benign (Jan 13, 2018)
13-50909965-C-T		Aicardi-Goutieres syndrome 2	Likely benign (May 26, 2021)
13-50909970-G-A		Aicardi-Goutieres syndrome 2	Uncertain significance (Jan 12, 2018)
13-50910073-CGGCATG-C		Aicardi-Goutieres syndrome 2	Uncertain significance (Oct 14, 2021)
13-50910078-T-C		Aicardi-Goutieres syndrome 2	Conflicting classifications of pathogenicity (Sep 01, 2021)
13-50910078-TG-T		Aicardi-Goutieres syndrome 2	Pathogenic (Aug 31, 2022)
13-50910079-G-A			Pathogenic (May 16, 2016)
13-50910080-G-C		Aicardi-Goutieres syndrome 2	Uncertain significance (Oct 25, 2022)
13-50910082-C-G		Aicardi-Goutieres syndrome 2	Likely benign (Aug 16, 2023)
13-50910085-T-G		Aicardi-Goutieres syndrome 2	Likely benign (Jun 20, 2023)
13-50910088-C-G		Aicardi-Goutieres syndrome 2	Likely benign (Mar 09, 2023)
13-50910091-G-T		Aicardi-Goutieres syndrome 2	Likely benign (Oct 13, 2023)
13-50910092-G-T		Aicardi-Goutieres syndrome 2	Uncertain significance (Apr 21, 2022)
13-50910094-C-T		Aicardi-Goutieres syndrome 2 • RNASEH2B-related disorder	Conflicting classifications of pathogenicity (Jan 19, 2023)
13-50910096-G-A		Aicardi-Goutieres syndrome 2	Uncertain significance (Aug 23, 2022)
13-50910097-C-T		Aicardi-Goutieres syndrome 2	Likely benign (Aug 09, 2023)
13-50910101-G-A		Aicardi-Goutieres syndrome 2	Uncertain significance (Aug 10, 2023)
13-50910101-G-C		Aicardi-Goutieres syndrome 2	Uncertain significance (Sep 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASEH2B	protein_coding	protein_coding	ENST00000336617	11	60779

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.26e-9	0.315	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.239	154	146	1.06	0.00000666	2039
Missense in Polyphen		46	43.356	1.061		644
Synonymous	-0.228	53	50.9	1.04	0.00000231	545
Loss of Function	0.760	15	18.5	0.810	7.76e-7	266

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000483	0.000483
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000220	0.000202
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non catalytic subunit of RNase H2, 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}.
• Pathway: DNA replication - Homo sapiens (human) (Consensus)

Intolerance Scores

• loftool: 0.193
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.239
• ghis: 0.554

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.275

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnaseh2b
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; embryo phenotype; liver/biliary system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: in utero embryonic development;RNA catabolic process;ribonucleotide metabolic process;regulation of G2/M transition of mitotic cell cycle;negative regulation of gene expression;positive regulation of fibroblast proliferation;RNA phosphodiester bond hydrolysis, endonucleolytic;regulation of DNA damage checkpoint
• Cellular component: nucleus;nucleoplasm;ribonuclease H2 complex
• Molecular function: RNA-DNA hybrid ribonuclease activity