rs2156323

Positions:

• chr9-133855699-G-A

Variant summary

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

The NM_001134398.2(VAV2):​c.380+5675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,256 control chromosomes in the GnomAD database, including 817 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 0.093 (817 hom., cov: 33)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.67

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.380+5675C>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.380+5675C>T		intron_variant		1	NM_001134398.2	ENSP00000360916	A1
VAV2	ENST00000406606.7	c.380+5675C>T		intron_variant		1		ENSP00000385362	P4
VAV2	ENST00000371851.1	c.380+5675C>T		intron_variant		5		ENSP00000360917	A1

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14178 AN: 152138 Hom.: 817 Cov.: 33

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.0818

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

GnomAD4 genome AF: 0.0930 AC: 14157 AN: 152256 Hom.: 817 Cov.: 33 AF XY: 0.0931 AC XY: 6929 AN XY: 74442

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.0805

Alfa AF: 0.102 Hom.: 148

Bravo AF: 0.0878

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.64

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: rs2156323; hg19: chr9-136720821;