rs12344583

Positions:

• chr9-133858398-A-G

Variant summary

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

The NM_001134398.2(VAV2):​c.380+2976T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,112 control chromosomes in the GnomAD database, including 7,569 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 0.28 (7569 hom., cov: 33)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV2	NM_001134398.2	c.380+2976T>C		intron_variant		ENST00000371850.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV2	ENST00000371850.8	c.380+2976T>C		intron_variant		1	NM_001134398.2	A1
VAV2	ENST00000406606.7	c.380+2976T>C		intron_variant		1		P4
VAV2	ENST00000371851.1	c.380+2976T>C		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42827 AN: 151994 Hom.: 7545 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.282 AC: 42888 AN: 152112 Hom.: 7569 Cov.: 33 AF XY: 0.280 AC XY: 20799 AN XY: 74368

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.236

Alfa AF: 0.212 Hom.: 6450

Bravo AF: 0.295

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.26

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: rs12344583; hg19: chr9-136723520;