RASGRP2

RAS guanyl releasing protein 2, the group of EF-hand domain containing

Basic information

Region (hg38): 11:64726911-64745456

Links

ENSG00000068831 ∙ NCBI:10235 ∙ OMIM:605577 ∙ HGNC:9879 ∙ Uniprot:Q7LDG7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• platelet-type bleeding disorder 18 (Supportive), mode of inheritance: AR
• platelet-type bleeding disorder 18 (Definitive), mode of inheritance: AR
• osteopetrosis (Strong), mode of inheritance: AR
• platelet-type bleeding disorder 18 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bleeding disorder, platelet-type, 18	AR	Hematologic	Individuals may demonstrate a bleeding diathesis (including postraumatic/postsurgical), and surveillance and prompt treatment of bleeding episodes may be beneficial	Hematologic	24958846

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RASGRP2 gene.

• not provided (6 variants)
• Platelet-type bleeding disorder 18 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RASGRP2 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	5	45
missense	1	6	50	3		60
nonsense	3					3
start loss						0
frameshift	5	1				6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		4				4
splice region		2	5	8	4	19
non coding			1	25	30	56
Total	9	11	52	68	35

Highest pathogenic variant AF is 0.00000658

Variants in RASGRP2

This is a list of pathogenic ClinVar variants found in the RASGRP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-64727311-G-C			Uncertain significance (Oct 10, 2016)
11-64727322-C-A		Inborn genetic diseases	Uncertain significance (Oct 01, 2024)
11-64727335-C-T		RASGRP2-related disorder	Benign (Mar 14, 2023)
11-64727344-C-T			Conflicting classifications of pathogenicity (Feb 23, 2023)
11-64727354-C-T		Inborn genetic diseases • not specified	Uncertain significance (Sep 30, 2024)
11-64727355-G-A		not specified	Conflicting classifications of pathogenicity (Feb 06, 2024)
11-64727506-AT-A			Benign (Oct 05, 2019)
11-64727506-ATT-A			Benign (Oct 05, 2019)
11-64727506-ATTTT-A			Benign (Oct 05, 2019)
11-64728680-G-A			Benign (Jul 15, 2018)
11-64728856-C-G			Likely benign (Aug 16, 2023)
11-64728885-G-T		not specified	Benign (Jan 31, 2024)
11-64728893-G-A			Uncertain significance (May 31, 2022)
11-64728915-G-A			Likely benign (Jan 25, 2023)
11-64728916-C-A			Likely benign (Nov 01, 2023)
11-64728917-G-A		Platelet-type bleeding disorder 18	Uncertain significance (-)
11-64728950-G-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
11-64728986-G-A			Uncertain significance (Sep 27, 2022)
11-64729007-G-A		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
11-64729045-G-T		not specified	Benign (Jan 22, 2024)
11-64729049-G-A			Likely benign (Jan 30, 2023)
11-64729115-T-C			Benign (Jul 09, 2018)
11-64729272-C-T			Benign (Jul 15, 2018)
11-64729273-G-A			Likely benign (Jul 10, 2018)
11-64729494-G-A			Benign (Jul 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RASGRP2	protein_coding	protein_coding	ENST00000354024	15	18546

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.244	0.756	125724	0	23	125747	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	294	375	0.784	0.0000255	3948
Missense in Polyphen		87	113.98	0.76327		1187
Synonymous	0.445	146	153	0.954	0.00000992	1202
Loss of Function	3.83	7	29.4	0.238	0.00000155	330

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.000217	0.000217
South Asian	0.0000981	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. {ECO:0000269|PubMed:10918068, ECO:0000269|PubMed:14702343, ECO:0000269|PubMed:17576779, ECO:0000269|PubMed:17702895, ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135}.
• Disease: DISEASE: Bleeding disorder, platelet-type 18 (BDPLT18) [MIM:615888]: A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. {ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135, ECO:0000269|PubMed:28726538, ECO:0000269|PubMed:28762304}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Platelet activation - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);MAPK Signaling Pathway;Chemokine signaling pathway;Ras Signaling;Signaling by GPCR;Regulation of Ras family activation;Signal Transduction;Integrin alphaIIb beta3 signaling;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Rap1 signalling;Adaptive Immune System;Platelet Aggregation (Plug Formation);Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;Integrin signaling;Hemostasis;FCERI mediated NF-kB activation;G alpha (q) signalling events;GPCR downstream signalling;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.152

Intolerance Scores

• loftool: 0.341
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.46

Haploinsufficiency Scores

• pHI: 0.400
• hipred: Y
• hipred_score: 0.785
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.895

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rasgrp2
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: regulation of cell growth;signal transduction;Ras protein signal transduction;positive regulation of GTPase activity;cellular response to calcium ion
• Cellular component: cytosol;plasma membrane;cell junction;ruffle membrane;neuron projection;synapse
• Molecular function: guanyl-nucleotide exchange factor activity;calcium ion binding;lipid binding;diacylglycerol binding