9-133763648-T-C

Variant names:

• chr9-133763648-T-C
• rs509590
• NM_001134398.2:c.*414A>G

Variant summary

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

The NM_001134398.2(VAV2):​c.*414A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 206,800 control chromosomes in the GnomAD database, including 24,349 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 0.43 (16413 hom., cov: 32)
  • Exomes 𝑓: 0.53 (7936 hom.)
• Consequence: VAV2 NM_001134398.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134398.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV2	NM_001134398.2	MANE Select	c.*414A>G		3_prime_UTR	Exon 30 of 30	NP_001127870.1	P52735-1
	VAV2	NM_001411028.1		c.*414A>G		3_prime_UTR	Exon 28 of 28	NP_001397957.1	P52735-2
	VAV2	NM_003371.4		c.*414A>G		3_prime_UTR	Exon 27 of 27	NP_003362.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV2	ENST00000371850.8	TSL:1 MANE Select	c.*414A>G		3_prime_UTR	Exon 30 of 30	ENSP00000360916.3	P52735-1
	VAV2	ENST00000406606.7	TSL:1	c.*414A>G		3_prime_UTR	Exon 27 of 27	ENSP00000385362.3	P52735-3
	VAV2	ENST00000876887.1		c.*414A>G		3_prime_UTR	Exon 27 of 27	ENSP00000546946.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65090 AN: 151918 Hom.: 16407 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.499

GnomAD4 exome AF: 0.526 AC: 28783 AN: 54764 Hom.: 7936 Cov.: 0 AF XY: 0.526 AC XY: 15070 AN XY: 28650

African (AFR) AF: 0.167 AC: 208 AN: 1248

American (AMR) AF: 0.585 AC: 1890 AN: 3230

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 825 AN: 1322

East Asian (EAS) AF: 0.897 AC: 1841 AN: 2052

South Asian (SAS) AF: 0.537 AC: 3805 AN: 7088

European-Finnish (FIN) AF: 0.411 AC: 1269 AN: 3086

Middle Eastern (MID) AF: 0.609 AC: 157 AN: 258

European-Non Finnish (NFE) AF: 0.515 AC: 17141 AN: 33314

Other (OTH) AF: 0.520 AC: 1647 AN: 3166

GnomAD4 genome AF: 0.428 AC: 65103 AN: 152036 Hom.: 16413 Cov.: 32 AF XY: 0.432 AC XY: 32080 AN XY: 74298

African (AFR) AF: 0.171 AC: 7090 AN: 41492

American (AMR) AF: 0.544 AC: 8306 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2199 AN: 3472

East Asian (EAS) AF: 0.876 AC: 4522 AN: 5160

South Asian (SAS) AF: 0.518 AC: 2491 AN: 4806

European-Finnish (FIN) AF: 0.424 AC: 4485 AN: 10576

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.507 AC: 34476 AN: 67940

Other (OTH) AF: 0.499 AC: 1054 AN: 2112

Alfa AF: 0.462 Hom.: 7310

Bravo AF: 0.431

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.65
PhyloP100		-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: rs509590; hg19: chr9-136628770; COSMIC: COSV58306156;