9-133769469-A-C

Position:

• chr9-133769469-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001134398.2(VAV2):​c.2382T>G​(p.Ser794Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 32)
• Consequence: VAV2 NM_001134398.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39076483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.2382T>G	p.Ser794Arg	missense_variant	28/30	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.2382T>G	p.Ser794Arg	missense_variant	28/30	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.2318-873T>G		intron_variant		1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.2352T>G	p.Ser784Arg	missense_variant	26/28	5		ENSP00000360917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.2382T>G (p.S794R) alteration is located in exon 28 (coding exon 28) of the VAV2 gene. This alteration results from a T to G substitution at nucleotide position 2382, causing the serine (S) at amino acid position 794 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;.
Eigen	Benign	-0.075
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.27
Sift	Benign	0.068	T;T
Sift4G	Uncertain	0.043	D;D
Polyphen		0.93	P;.
Vest4		0.55
MutPred		0.20		Loss of phosphorylation at S794 (P = 0.0601);.;
MVP		0.70
MPC		0.66
ClinPred		0.76	D
GERP RS		1.9
Varity_R		0.11
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-136634591;