NM_001134398.2:c.2548G>A

Variant names:

• chr9-133768483-C-T
• rs150483592
• NM_001134398.2:c.2548G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001134398.2(VAV2):​c.2548G>A​(p.Gly850Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: VAV2 NM_001134398.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30267245).
• BS2: High AC in GnomAd4 at 19 AD gene.

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.2548G>A	p.Gly850Ser	missense	Exon 29 of 30	NP_001127870.1	P52735-1
	VAV2	NM_001411028.1		c.2518G>A	p.Gly840Ser	missense	Exon 27 of 28	NP_001397957.1	P52735-2
	VAV2	NM_003371.4		c.2431G>A	p.Gly811Ser	missense	Exon 26 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.2548G>A	p.Gly850Ser	missense	Exon 29 of 30	ENSP00000360916.3	P52735-1
	VAV2	ENST00000406606.7	TSL:1	c.2431G>A	p.Gly811Ser	missense	Exon 26 of 27	ENSP00000385362.3	P52735-3
	VAV2	ENST00000876887.1		c.2671G>A	p.Gly891Ser	missense	Exon 26 of 27	ENSP00000546946.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251196 AF XY: 0.0000589

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461684 Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20 AN XY: 727168

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1112000

Other (OTH) AF: 0.000116 AC: 7 AN: 60390

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74414

African (AFR) AF: 0.000433 AC: 18 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000140

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000115 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.010	N
PhyloP100		7.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.90	N
REVEL	Uncertain	0.32
Sift	Benign	0.49	T
Sift4G	Benign	0.37	T
Polyphen		1.0	D
Vest4		0.79
MVP		0.60
MPC		1.0
ClinPred		0.14	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.62
Mutation Taster		=28/72	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: rs150483592; hg19: chr9-136633605;