chr9-133810892-T-C

Variant names:

• chr9-133810892-T-C
• rs7021663
• NM_001134398.2:c.553-687A>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.553-687A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,196 control chromosomes in the GnomAD database, including 6,787 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 (6787 hom., cov: 33)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.553-687A>G		intron_variant	Intron 5 of 29	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.553-687A>G		intron_variant	Intron 5 of 29	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.552+1222A>G		intron_variant	Intron 5 of 26	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.552+1222A>G		intron_variant	Intron 5 of 27	5		ENSP00000360917.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42381 AN: 152078 Hom.: 6769 Cov.: 33

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.279 AC: 42451 AN: 152196 Hom.: 6787 Cov.: 33 AF XY: 0.277 AC XY: 20575 AN XY: 74396

African (AFR) AF: 0.446 AC: 18502 AN: 41524

American (AMR) AF: 0.282 AC: 4315 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3470

East Asian (EAS) AF: 0.0774 AC: 400 AN: 5170

South Asian (SAS) AF: 0.240 AC: 1159 AN: 4820

European-Finnish (FIN) AF: 0.217 AC: 2305 AN: 10606

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14281 AN: 68002

Other (OTH) AF: 0.245 AC: 516 AN: 2108

Alfa AF: 0.236 Hom.: 14396

Bravo AF: 0.290

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.50
PhyloP100		-0.15
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: rs7021663; hg19: chr9-136676014;