9-133817286-G-A

Position:

• chr9-133817286-G-A

Variant summary

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

The ENST00000371850.8(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 ENST00000371850.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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 (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.450-5070C>T		intron_variant		ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.450-5070C>T		intron_variant		1	NM_001134398.2	ENSP00000360916	A1
VAV2	ENST00000406606.7	c.450-5070C>T		intron_variant		1		ENSP00000385362	P4
VAV2	ENST00000371851.1	c.450-5070C>T		intron_variant		5		ENSP00000360917	A1

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.143

Alfa AF: 0.155 Hom.: 3050

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7026263; hg19: chr9-136682408;