NM_001134398.2:c.321+34337C>T

Variant names:

• chr9-133904766-G-A
• rs2789823
• NM_001134398.2:c.321+34337C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.321+34337C>T		intron_variant	Intron 2 of 29	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.321+34337C>T		intron_variant	Intron 2 of 29	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.321+34337C>T		intron_variant	Intron 2 of 26	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.321+34337C>T		intron_variant	Intron 2 of 27	5		ENSP00000360917.1
VAV2	ENST00000486113.1	n.302+34337C>T		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.218 AC: 9035 AN: 41532

American (AMR) AF: 0.908 AC: 13901 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3459 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.996 AC: 4814 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10632 AN: 10632

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67783 AN: 68032

Other (OTH) AF: 0.846 AC: 1786 AN: 2112

Alfa AF: 0.922 Hom.: 112892

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
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2789823; hg19: chr9-136769888;