Variant chr9-133769432-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001134398.2(VAV2):c.2419G>A(p.Ala807Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,612,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

VAV2
NM_001134398.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

Variant links:

Genes affected

VAV2 (HGNC:12658): (vav guanine nucleotide exchange factor 2) 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]

VAV2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017631859).

BS2

High AC in GnomAd4 at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2 link	c.2419G>A	p.Ala807Thr	missense_variant	28/30	ENST00000371850.8	NP_001127870.1	P52735-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VAV2	ENST00000371850.8 link	c.2419G>A	p.Ala807Thr	missense_variant	28/30	1	NM_001134398.2	ENSP00000360916.3	P52735-1
VAV2	ENST00000406606.7 link	c.2318-836G>A		intron_variant		1		ENSP00000385362.3	P52735-3
VAV2	ENST00000371851.1 link	c.2389G>A	p.Ala797Thr	missense_variant	26/28	5		ENSP00000360917.1	P52735-2

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000437

AC:

107

AN:

244604

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

133266

show subpopulations

Gnomad AFR exome

AF:

0.000403

Gnomad AMR exome

AF:

0.0000879

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000858

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.00110

AC:

1604

AN:

1460098

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

773

AN XY:

726138

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.0000898

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.000713

GnomAD4 genome

AF:

0.000656

AC:

100

AN:

152328

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000937

Hom.:

Bravo

AF:

0.000604

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000382

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000774

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2024

The c.2419G>A (p.A807T) alteration is located in exon 28 (coding exon 28) of the VAV2 gene. This alteration results from a G to A substitution at nucleotide position 2419, causing the alanine (A) at amino acid position 807 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.062

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.050

Sift

Benign

0.62

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0020

B;.

Vest4

0.14

MVP

0.27

MPC

0.30

ClinPred

0.038

GERP RS

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.069

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over