rs7026263

Variant names:

• chr9-133817286-G-A
• rs7026263
• NM_001134398.2:c.450-5070C>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.450-5070C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,018 control chromosomes in the GnomAD database, including 2,582 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 0.18 (2582 hom., cov: 33)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.450-5070C>T		intron_variant	Intron 4 of 29	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.450-5070C>T		intron_variant	Intron 4 of 29	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.450-5070C>T		intron_variant	Intron 4 of 26	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.450-5070C>T		intron_variant	Intron 4 of 27	5		ENSP00000360917.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26893 AN: 151900 Hom.: 2577 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.177 AC: 26937 AN: 152018 Hom.: 2582 Cov.: 33 AF XY: 0.176 AC XY: 13103 AN XY: 74284

African (AFR) AF: 0.236 AC: 9786 AN: 41416

American (AMR) AF: 0.208 AC: 3170 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3472

East Asian (EAS) AF: 0.0206 AC: 107 AN: 5186

South Asian (SAS) AF: 0.191 AC: 921 AN: 4816

European-Finnish (FIN) AF: 0.146 AC: 1541 AN: 10564

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10390 AN: 67988

Other (OTH) AF: 0.143 AC: 302 AN: 2114

Alfa AF: 0.159 Hom.: 6955

Bravo AF: 0.183

Asia WGS AF: 0.109 AC: 381 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	3.2
DANN	Benign	0.59
PhyloP100		-0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7026263; hg19: chr9-136682408;