VAV2

protein-coding

vav guanine nucleotide exchange factor 2, the group of Dbl family Rho GEFs|SH2 domain containing|Pleckstrin homology domain containing

Gene summary

VAV2 is the second member of the VAV guanine nucleotide exchange factor family of oncogenes. Unlike VAV1, which is expressed exclusively in hematopoietic cells, VAV2 transcripts were found in most tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

MANE transcript

NM_001134398.2

Inheritance

—

ClinVar variants

U:150B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr9:133,761,894-133,992,604

External References & Databases

Ensembl (ENSG00000160293)

Transcript & Mutation Effects

hg38 • Region Span ~230.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VAV2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 15

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001134398.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	9 clinvar	5 clinvar	18
missense			133 clinvar	2 clinvar		135
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	150	11	5	166

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001134398.2	RefSeq	NP_001127870.1	30	MANE Select
ENST00000371850.8	Ensembl	ENSP00000360916.3	30	MANE Select
NM_001411028.1	RefSeq	NP_001397957.1	28	Standard
NM_003371.4	RefSeq	NP_003362.2	27	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Focal adhesion - Homo sapiens (human)
T cell receptor signaling pathway - Homo sapiens (human)
B cell receptor signaling pathway - Homo sapiens (human)
Fc epsilon RI signaling pathway - Homo sapiens (human)
Fc gamma R-mediated phagocytosis - Homo sapiens (human)

Biological Process

angiogenesis
signal transduction
G protein-coupled receptor signaling pathway
small GTPase mediated signal transduction
regulation of cell size

Molecular Function

phosphotyrosine residue binding
guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
epidermal growth factor receptor binding
protein binding

Cellular Component

cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371850
Coding exons: 30
Length: 230711
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.49	436	533	0.819	0.0000324	5817
Missense (PolyPhen)		125	193.22	0.64692		2145
Synonymous	-0.868	237	221	1.07	0.0000151	1567
Loss of Function	4.44	20	55.8	0.358	0.00000255	655

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.301

Intolerance Scores

LoFtool: 0.198
RVIS EVS: -1.7
RVIS percentile EVS: 2.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.953

Gene Damage Prediction

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