Variant 9-133775000-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001134398.2(VAV2):c.2070C>T(p.His690His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,613,484 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 166 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 175 hom. )

Consequence

VAV2
NM_001134398.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0210

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-133775000-G-A is Benign according to our data. Variant chr9-133775000-G-A is described in ClinVar as [Benign]. Clinvar id is 780826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.021 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2 linkuse as main transcript	c.2070C>T	p.His690His	synonymous_variant	25/30	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.2070C>T	p.His690His	synonymous_variant	25/30	1	NM_001134398.2	ENSP00000360916.3	P52735-1
VAV2	ENST00000406606.7 linkuse as main transcript	c.2040C>T	p.His680His	synonymous_variant	23/27	1		ENSP00000385362.3	P52735-3
VAV2	ENST00000371851.1 linkuse as main transcript	c.2040C>T	p.His680His	synonymous_variant	23/28	5		ENSP00000360917.1	P52735-2

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3992

AN:

152150

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00720

AC:

1797

AN:

249690

Hom.:

AF XY:

0.00538

AC XY:

728

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.0942

Gnomad AMR exome

AF:

0.00595

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.00345

GnomAD4 exome

AF:

0.00289

AC:

4224

AN:

1461216

Hom.:

175

Cov.:

AF XY:

0.00258

AC XY:

1878

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.0980

Gnomad4 AMR exome

AF:

0.00633

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.00663

GnomAD4 genome

AF:

0.0263

AC:

4012

AN:

152268

Hom.:

166

Cov.:

AF XY:

0.0243

AC XY:

1809

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0310

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.4

DANN

Benign

0.39

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