rs669443

Variant names:

• chr9-133776591-C-T
• rs669443
• NM_001134398.2:c.1966-511G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134398.2(VAV2):​c.1966-511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,976 control chromosomes in the GnomAD database, including 13,948 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 0.42 (13948 hom., cov: 32)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.1966-511G>A		intron_variant	Intron 23 of 29	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.1966-511G>A		intron_variant	Intron 23 of 29	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.1936-511G>A		intron_variant	Intron 21 of 26	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.1936-511G>A		intron_variant	Intron 21 of 27	5		ENSP00000360917.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63504 AN: 151858 Hom.: 13934 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.418 AC: 63543 AN: 151976 Hom.: 13948 Cov.: 32 AF XY: 0.410 AC XY: 30438 AN XY: 74292

African (AFR) AF: 0.482 AC: 19998 AN: 41450

American (AMR) AF: 0.326 AC: 4992 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1465 AN: 3464

East Asian (EAS) AF: 0.0380 AC: 196 AN: 5156

South Asian (SAS) AF: 0.409 AC: 1965 AN: 4810

European-Finnish (FIN) AF: 0.372 AC: 3940 AN: 10578

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29606 AN: 67918

Other (OTH) AF: 0.432 AC: 911 AN: 2108

Alfa AF: 0.431 Hom.: 7461

Bravo AF: 0.412

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.51
PhyloP100		1.6
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: rs669443; hg19: chr9-136641713; COSMIC: COSV64080893;