rs2789823

chr9-133904766-G-Achr9-133904766-G-Cchr9-133904766-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134398.2(VAV2):c.321+34337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,306 control chromosomes in the GnomAD database, including 54,676 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (54676 hom., cov: 35)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV2	NM_001134398.2	c.321+34337C>T		intron_variant		ENST00000371850.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV2	ENST00000371850.8	c.321+34337C>T		intron_variant		1	NM_001134398.2	A1
VAV2	ENST00000406606.7	c.321+34337C>T		intron_variant		1		P4
VAV2	ENST00000371851.1	c.321+34337C>T		intron_variant		5		A1
VAV2	ENST00000486113.1	n.302+34337C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117769 AN: 152188 Hom.: 54670 Cov.: 35

Gnomad AFR AF: 0.218

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.844

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.773 AC: 117780 AN: 152306 Hom.: 54676 Cov.: 35 AF XY: 0.782 AC XY: 58240 AN XY: 74484

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.846

Alfa AF: 0.974 Hom.: 84259

Bravo AF: 0.741

Asia WGS AF: 0.952 AC: 3309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs2789823; hg19: chr9-136769888;