rs756777

Positions:

• chr9-133813958-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.450-1742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,192 control chromosomes in the GnomAD database, including 6,745 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 (6745 hom., cov: 33)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46

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 = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV2	NM_001134398.2	c.450-1742T>C		intron_variant		ENST00000371850.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV2	ENST00000371850.8	c.450-1742T>C		intron_variant		1	NM_001134398.2	A1
VAV2	ENST00000406606.7	c.450-1742T>C		intron_variant		1		P4
VAV2	ENST00000371851.1	c.450-1742T>C		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42257 AN: 152074 Hom.: 6729 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.278 AC: 42320 AN: 152192 Hom.: 6745 Cov.: 33 AF XY: 0.276 AC XY: 20532 AN XY: 74414

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0777

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.243

Alfa AF: 0.237 Hom.: 2287

Bravo AF: 0.290

Asia WGS AF: 0.195 AC: 680 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	0.029
DANN	Benign	0.16

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: rs756777; hg19: chr9-136679080;