RRAS2

RAS related 2, the group of RAS type GTPase family

Basic information

Region (hg38): 11:14277922-14364506

Links

ENSG00000133818 ∙ NCBI:22800 ∙ OMIM:600098 ∙ HGNC:17271 ∙ Uniprot:P62070 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• noonan syndrome 12 (Strong), mode of inheritance: AD
• noonan syndrome 12 (Strong), mode of inheritance: AD
• Noonan syndrome (Supportive), mode of inheritance: AD
• noonan syndrome 12 (Moderate), mode of inheritance: AD
• ovarian cancer (No Known Disease Relationship), mode of inheritance: Unknown
• noonan syndrome 12 (Strong), mode of inheritance: AD
• Noonan syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Noonan syndrome 12	AD	Cardiovascular	Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and other congenital heart anomalies) can be beneficial	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	31130282; 31130285

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RRAS2 gene.

• Noonan syndrome (4 variants)
• not provided (3 variants)
• Noonan syndrome 12 (3 variants)
• Neoplasm of ovary (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RRAS2 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				10	1	11
missense	3	3	25		1	32
nonsense						0
start loss						0
frameshift						0
inframe indel	2	1				3
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1	2	4
non coding			5	2	5	12
Total	5	4	31	12	7

Variants in RRAS2

This is a list of pathogenic ClinVar variants found in the RRAS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-14279213-C-G			Benign (May 14, 2021)
11-14279343-A-G			Likely benign (Nov 20, 2021)
11-14279346-G-C			Likely benign (Nov 27, 2023)
11-14279356-C-G			Uncertain significance (Nov 15, 2022)
11-14279371-T-C		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
11-14279381-G-A			Uncertain significance (Jan 29, 2024)
11-14279392-G-C		Noonan syndrome 12	Uncertain significance (May 16, 2023)
11-14279400-A-G			Benign (Jan 17, 2024)
11-14279426-T-G			Uncertain significance (Jan 01, 2023)
11-14279442-C-A			Likely benign (Mar 29, 2023)
11-14281610-C-T			Likely benign (Sep 01, 2024)
11-14281612-G-A			Uncertain significance (Jan 22, 2024)
11-14281640-A-T			Uncertain significance (Mar 05, 2024)
11-14281645-T-C		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
11-14281676-T-C			Likely benign (Sep 18, 2023)
11-14281678-C-T			Uncertain significance (Jan 29, 2024)
11-14281680-T-G		RRAS2-related disorder • Inborn genetic diseases	Uncertain significance (Dec 29, 2022)
11-14281689-C-T		Noonan syndrome	Uncertain significance (May 07, 2024)
11-14281690-G-A		Noonan syndrome 12 • RRAS2-related disorder	Uncertain significance (Dec 01, 2023)
11-14281717-T-A			Benign (Jul 17, 2021)
11-14281736-T-A		Noonan syndrome 12 • RASopathy	Benign (Sep 17, 2024)
11-14294369-C-T			Benign (May 14, 2021)
11-14294372-A-AT			Benign (May 14, 2021)
11-14294477-T-C			Likely benign (Mar 28, 2022)
11-14294515-T-A			Uncertain significance (Nov 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RRAS2	protein_coding	protein_coding	ENST00000256196	6	86581

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.975	0.0253	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	59	112	0.527	0.00000587	1332
Missense in Polyphen		15	46.307	0.32393		552
Synonymous	1.07	30	38.5	0.780	0.00000186	364
Loss of Function	3.12	0	11.3	0.00	4.78e-7	141

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: It is a plasma membrane-associated GTP-binding protein with GTPase activity. Might transduce growth inhibitory signals across the cell membrane, exerting its effect through an effector shared with the Ras proteins but in an antagonistic fashion.
• Disease: DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269|PubMed:8052619}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Autophagy - animal - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Cellular senescence - Homo sapiens (human);MAPK Signaling Pathway;Ras Signaling;Regulation of Actin Cytoskeleton (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.284
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.25

Haploinsufficiency Scores

• pHI: 0.848
• hipred: Y
• hipred_score: 0.783
• ghis: 0.623

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.887

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rras2
• Phenotype: immune system phenotype; vision/eye 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); hematopoietic system phenotype; neoplasm; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: osteoblast differentiation;Ras protein signal transduction;positive regulation of cell migration;regulation of neuron death
• Cellular component: endoplasmic reticulum;plasma membrane;focal adhesion;membrane;extracellular exosome
• Molecular function: GTPase activity;protein binding;GTP binding