Variant 9-133776061-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001134398.2(VAV2):c.1985C>T(p.Pro662Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

VAV2
NM_001134398.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14375478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2 linkuse as main transcript	c.1985C>T	p.Pro662Leu	missense_variant	24/30	ENST00000371850.8	NP_001127870.1	P52735-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VAV2	ENST00000371850.8 linkuse as main transcript	c.1985C>T	p.Pro662Leu	missense_variant	24/30	1	NM_001134398.2	ENSP00000360916.3	P52735-1
VAV2	ENST00000406606.7 linkuse as main transcript	c.1955C>T	p.Pro652Leu	missense_variant	22/27	1		ENSP00000385362.3	P52735-3
VAV2	ENST00000371851.1 linkuse as main transcript	c.1955C>T	p.Pro652Leu	missense_variant	22/28	5		ENSP00000360917.1	P52735-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Sep 10, 2024

The c.1985C>T (p.P662L) alteration is located in exon 24 (coding exon 24) of the VAV2 gene. This alteration results from a C to T substitution at nucleotide position 1985, causing the proline (P) at amino acid position 662 to be replaced by a leucine (L). 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

0.061

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.070

.;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.0076

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.054

T;T;T

Sift4G

Benign

0.69

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.24

MutPred

0.31

.;Loss of disorder (P = 0.0244);.;

MVP

0.37

MPC

0.31

ClinPred

0.35

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.32

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