9-133775000-G-C

Variant names:

• chr9-133775000-G-C
• rs7875953
• NM_001134398.2:c.2070C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134398.2(VAV2):​c.2070C>G​(p.His690Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H690H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VAV2 NM_001134398.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134398.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV2	NM_001134398.2	MANE Select	c.2070C>G	p.His690Gln	missense	Exon 25 of 30	NP_001127870.1	P52735-1
	VAV2	NM_001411028.1		c.2040C>G	p.His680Gln	missense	Exon 23 of 28	NP_001397957.1	P52735-2
	VAV2	NM_003371.4		c.2040C>G	p.His680Gln	missense	Exon 23 of 27	NP_003362.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV2	ENST00000371850.8	TSL:1 MANE Select	c.2070C>G	p.His690Gln	missense	Exon 25 of 30	ENSP00000360916.3	P52735-1
	VAV2	ENST00000406606.7	TSL:1	c.2040C>G	p.His680Gln	missense	Exon 23 of 27	ENSP00000385362.3	P52735-3
	VAV2	ENST00000876887.1		c.2280C>G	p.His760Gln	missense	Exon 23 of 27	ENSP00000546946.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	-0.19	N
PhyloP100		-0.021
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.81	N
REVEL	Uncertain	0.58
Sift	Benign	0.036	D
Sift4G	Benign	0.077	T
Polyphen		0.51	P
Vest4		0.67
MutPred		0.30		Gain of ubiquitination at K688 (P = 0.0561)
MVP		0.74
MPC		0.89
ClinPred		0.92	D
GERP RS		-3.2
Varity_R		0.36
gMVP		0.62
Mutation Taster		=30/70	disease causing

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: rs7875953; hg19: chr9-136640122;