Variant 9-133779937-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001134398.2(VAV2):c.1743C>T(p.Asp581=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,612,426 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 5 hom. )

Consequence

VAV2
NM_001134398.2 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.08

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-133779937-G-A is Benign according to our data. Variant chr9-133779937-G-A is described in ClinVar as [Benign]. Clinvar id is 711533.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.08 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (891/152324) while in subpopulation AFR AF= 0.02 (833/41564). AF 95% confidence interval is 0.0189. There are 9 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 891 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV2	NM_001134398.2 linkuse as main transcript	c.1743C>T	p.Asp581=	splice_region_variant, synonymous_variant	21/30	ENST00000371850.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV2	ENST00000371850.8 linkuse as main transcript	c.1743C>T	p.Asp581=	splice_region_variant, synonymous_variant	21/30	1	NM_001134398.2	A1	P52735-1
VAV2	ENST00000406606.7 linkuse as main transcript	c.1713C>T	p.Asp571=	splice_region_variant, synonymous_variant	19/27	1		P4	P52735-3
VAV2	ENST00000371851.1 linkuse as main transcript	c.1713C>T	p.Asp571=	splice_region_variant, synonymous_variant	19/28	5		A1	P52735-2

Frequencies

GnomAD3 genomes

AF:

0.00576

AC:

876

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00164

AC:

410

AN:

249510

Hom.:

AF XY:

0.00120

AC XY:

162

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.0208

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000698

AC:

1019

AN:

1460102

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

431

AN XY:

726322

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00295

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.00585

AC:

891

AN:

152324

Hom.:

Cov.:

AF XY:

0.00567

AC XY:

422

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.00672

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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