9-133763648-T-C

Position:

• chr9-133763648-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.*414A>G		3_prime_UTR_variant	30/30	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.*414A>G		3_prime_UTR_variant	30/30	1	NM_001134398.2	ENSP00000360916	A1
VAV2	ENST00000406606.7	c.*414A>G		3_prime_UTR_variant	27/27	1		ENSP00000385362	P4
VAV2	ENST00000371851.1	c.*414A>G		3_prime_UTR_variant	28/28	5		ENSP00000360917	A1

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

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.585

Gnomad4 ASJ exome AF: 0.624

Gnomad4 EAS exome AF: 0.897

Gnomad4 SAS exome AF: 0.537

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.520

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

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.499

Alfa AF: 0.460 Hom.: 6011

Bravo AF: 0.431

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.65

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: rs509590; hg19: chr9-136628770; COSMIC: COSV58306156;