chr9-133778872-T-C

Variant names:

• chr9-133778872-T-C
• rs602990
• NM_001134398.2:c.1780A>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.1780A>G​(p.Met594Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,612,324 control chromosomes in the GnomAD database, including 228,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (27668 hom., cov: 32)
  • Exomes 𝑓: 0.51 (200439 hom.)
• Consequence: VAV2 NM_001134398.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954
• Publications: 32 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 (MetaRNN=7.352029E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.1780A>G	p.Met594Val	missense_variant	Exon 22 of 30	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.1780A>G	p.Met594Val	missense_variant	Exon 22 of 30	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.1750A>G	p.Met584Val	missense_variant	Exon 20 of 27	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.1750A>G	p.Met584Val	missense_variant	Exon 20 of 28	5		ENSP00000360917.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88089 AN: 151934 Hom.: 27615 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.555

GnomAD2 exomes AF: 0.492 AC: 123079 AN: 250134 AF XY: 0.495

Gnomad AFR exome AF: 0.808

Gnomad AMR exome AF: 0.430

Gnomad ASJ exome AF: 0.503

Gnomad EAS exome AF: 0.0530

Gnomad FIN exome AF: 0.501

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.515 AC: 751513 AN: 1460272 Hom.: 200439 Cov.: 64 AF XY: 0.515 AC XY: 374048 AN XY: 726430

African (AFR) AF: 0.813 AC: 27224 AN: 33478

American (AMR) AF: 0.438 AC: 19586 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 13003 AN: 26130

East Asian (EAS) AF: 0.0338 AC: 1343 AN: 39698

South Asian (SAS) AF: 0.512 AC: 44168 AN: 86248

European-Finnish (FIN) AF: 0.502 AC: 26113 AN: 51996

Middle Eastern (MID) AF: 0.512 AC: 2954 AN: 5768

European-Non Finnish (NFE) AF: 0.527 AC: 585624 AN: 1111884

Other (OTH) AF: 0.522 AC: 31498 AN: 60360

GnomAD4 genome AF: 0.580 AC: 88199 AN: 152052 Hom.: 27668 Cov.: 32 AF XY: 0.570 AC XY: 42377 AN XY: 74328

African (AFR) AF: 0.799 AC: 33151 AN: 41486

American (AMR) AF: 0.496 AC: 7588 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1761 AN: 3468

East Asian (EAS) AF: 0.0528 AC: 273 AN: 5170

South Asian (SAS) AF: 0.500 AC: 2401 AN: 4802

European-Finnish (FIN) AF: 0.497 AC: 5257 AN: 10574

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36055 AN: 67952

Other (OTH) AF: 0.554 AC: 1166 AN: 2104

Alfa AF: 0.535 Hom.: 89009

Bravo AF: 0.584

TwinsUK AF: 0.521 AC: 1932

ALSPAC AF: 0.522 AC: 2011

ESP6500AA AF: 0.804 AC: 3543

ESP6500EA AF: 0.529 AC: 4549

ExAC AF: 0.500 AC: 60681

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.40
DANN	Benign	0.37
DEOGEN2	Benign	0.0	.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.53	T;T;T
MetaRNN	Benign	7.4e-7	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.
PhyloP100		0.95
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.97	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.81	T;T;T
Sift4G	Benign	0.44	T;T;T
Vest4		0.082
ClinPred		0.0015	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.12
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: rs602990; hg19: chr9-136643994; COSMIC: COSV64080812;