rs3780792

Positions:

• chr9-133970221-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.204+21854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,068 control chromosomes in the GnomAD database, including 6,887 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 0.29 (6887 hom., cov: 32)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.204+21854T>C		intron_variant		ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.204+21854T>C		intron_variant		1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.204+21854T>C		intron_variant		1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.204+21854T>C		intron_variant		5		ENSP00000360917.1
VAV2	ENST00000486113.1	n.185+21854T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43757 AN: 151950 Hom.: 6886 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.288 AC: 43758 AN: 152068 Hom.: 6887 Cov.: 32 AF XY: 0.292 AC XY: 21715 AN XY: 74338

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.282

Alfa AF: 0.324 Hom.: 14378

Bravo AF: 0.269

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.96
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3780792; hg19: chr9-136835343; COSMIC: COSV64081009;