rs602990

chr9-133778872-T-Achr9-133778872-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001134398.2(VAV2):c.1780A>T(p.Met594Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M594V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VAV2 NM_001134398.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.067685604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV2	NM_001134398.2	c.1780A>T	p.Met594Leu	missense_variant	22/30	ENST00000371850.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV2	ENST00000371850.8	c.1780A>T	p.Met594Leu	missense_variant	22/30	1	NM_001134398.2	A1
VAV2	ENST00000406606.7	c.1750A>T	p.Met584Leu	missense_variant	20/27	1		P4
VAV2	ENST00000371851.1	c.1750A>T	p.Met584Leu	missense_variant	20/28	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250134 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135498

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460386 Hom.: 0 Cov.: 64 AF XY: 0.00000138 AC XY: 1 AN XY: 726490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	13
Dann	Benign	0.76
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.068	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.32	N;N;N
REVEL	Benign	0.033
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.22
MutPred		0.38		.;Loss of sheet (P = 0.0457);.;
MVP		0.19
MPC		0.29
ClinPred		0.036	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.085
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs602990; hg19: chr9-136643994;