RASA2

RAS p21 protein activator 2, the group of C2 and RasGAP domain containing|Pleckstrin homology domain containing

Basic information

Region (hg38): 3:141487027-141615344

Links

ENSG00000155903 ∙ NCBI:5922 ∙ OMIM:601589 ∙ HGNC:9872 ∙ Uniprot:Q15283 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Noonan syndrome (Supportive), mode of inheritance: AD
• Noonan syndrome (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RASA2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RASA2 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			4	131	1	136
missense			248	4	1	253
nonsense			13			13
start loss						0
frameshift			14			14
inframe indel			10			10
splice donor/acceptor (+/-2bp)			12			12
splice region			11	22	3	36
non coding			9	94	35	138
Total	0	0	310	229	37

Variants in RASA2

This is a list of pathogenic ClinVar variants found in the RASA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-141487069-G-C		not specified	Uncertain significance (Sep 01, 2019)
3-141487069-G-T		not specified	Uncertain significance (Jan 06, 2020)
3-141487078-G-A		not specified	Uncertain significance (Jun 30, 2024)
3-141487085-T-TGGC			Conflicting classifications of pathogenicity (Dec 17, 2023)
3-141487085-T-TGGCGGCGGCGGCGCCTGCTGC			Uncertain significance (Jan 14, 2023)
3-141487086-G-GGCGGCGGCGGCGCCTGCTGCT		not specified	Conflicting classifications of pathogenicity (Jan 15, 2024)
3-141487086-G-GGCGGCGGCGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCT			Uncertain significance (Mar 26, 2022)
3-141487088-C-T			Uncertain significance (Sep 14, 2023)
3-141487089-GG-AT			Uncertain significance (Nov 25, 2023)
3-141487089-G-GGCGGCGGCGCCTGCTGCT			Uncertain significance (Sep 10, 2023)
3-141487092-G-T			Likely benign (Jan 31, 2024)
3-141487092-G-GGCGGCGCCTGCTGCT			Uncertain significance (Jan 27, 2024)
3-141487094-C-T		not specified	Uncertain significance (Feb 16, 2023)
3-141487095-G-A		RASA2-related disorder • not specified	Likely benign (Oct 20, 2019)
3-141487096-G-A		not specified	Uncertain significance (Jan 03, 2024)
3-141487096-G-C		not specified	Uncertain significance (Mar 29, 2023)
3-141487097-C-G			Uncertain significance (Jun 04, 2023)
3-141487096-G-GCGC			Uncertain significance (Apr 20, 2021)
3-141487098-G-A			Likely benign (Mar 01, 2022)
3-141487100-C-T		not specified • RASA2-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
3-141487102-G-C			Uncertain significance (Feb 24, 2023)
3-141487107-T-G		not specified	Likely benign (Feb 14, 2021)
3-141487108-G-T		not specified	Uncertain significance (Sep 15, 2021)
3-141487109-C-T		not specified • RASA2-related disorder	Benign/Likely benign (Jul 01, 2024)
3-141487110-G-A		not specified	Likely benign (Mar 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RASA2	protein_coding	protein_coding	ENST00000286364	24	128296

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.39e-31	0.000161	125664	0	83	125747	0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	309	417	0.741	0.0000202	5590
Missense in Polyphen		80	123.23	0.6492		1668
Synonymous	-0.542	155	147	1.06	0.00000737	1515
Loss of Function	0.394	48	51.0	0.941	0.00000284	644

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000903	0.000895
Ashkenazi Jewish	0.00	0.00
East Asian	0.000336	0.000326
Finnish	0.000374	0.000370
European (Non-Finnish)	0.000351	0.000343
Middle Eastern	0.000336	0.000326
South Asian	0.000170	0.000163
Other	0.000660	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4).
• Pathway: Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);MAPK Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Ras Signaling;Regulation of Ras family activation;Signal Transduction;Regulation of RAS by GAPs;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.2

Haploinsufficiency Scores

• pHI: 0.275
• hipred: Y
• hipred_score: 0.602
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.405

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rasa2

Gene ontology

• Biological process: MAPK cascade;signal transduction;positive regulation of GTPase activity;negative regulation of Ras protein signal transduction
• Cellular component: cytosol;perinuclear region of cytoplasm
• Molecular function: GTPase activator activity;phospholipid binding;metal ion binding