9-133775000-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001134398.2(VAV2):​c.2070C>T​(p.His690His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,613,484 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (166 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (175 hom.)
• Consequence: VAV2 NM_001134398.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0210
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 9-133775000-G-A is Benign according to our data. Variant chr9-133775000-G-A is described in ClinVar as Benign. ClinVar VariationId is 780826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.021 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

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>T	p.His690His	synonymous	Exon 25 of 30	NP_001127870.1	P52735-1
	VAV2	NM_001411028.1		c.2040C>T	p.His680His	synonymous	Exon 23 of 28	NP_001397957.1	P52735-2
	VAV2	NM_003371.4		c.2040C>T	p.His680His	synonymous	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>T	p.His690His	synonymous	Exon 25 of 30	ENSP00000360916.3	P52735-1
	VAV2	ENST00000406606.7	TSL:1	c.2040C>T	p.His680His	synonymous	Exon 23 of 27	ENSP00000385362.3	P52735-3
	VAV2	ENST00000876887.1		c.2280C>T	p.His760His	synonymous	Exon 23 of 27	ENSP00000546946.1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3992 AN: 152150 Hom.: 162 Cov.: 32

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00720 AC: 1797 AN: 249690 AF XY: 0.00538

Gnomad AFR exome AF: 0.0942

Gnomad AMR exome AF: 0.00595

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000329

Gnomad OTH exome AF: 0.00345

GnomAD4 exome AF: 0.00289 AC: 4224 AN: 1461216 Hom.: 175 Cov.: 31 AF XY: 0.00258 AC XY: 1878 AN XY: 726910

African (AFR) AF: 0.0980 AC: 3280 AN: 33468

American (AMR) AF: 0.00633 AC: 283 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.000661 AC: 57 AN: 86244

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52982

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1111888

Other (OTH) AF: 0.00663 AC: 400 AN: 60364

GnomAD4 genome AF: 0.0263 AC: 4012 AN: 152268 Hom.: 166 Cov.: 32 AF XY: 0.0243 AC XY: 1809 AN XY: 74460

African (AFR) AF: 0.0907 AC: 3766 AN: 41524

American (AMR) AF: 0.0112 AC: 172 AN: 15304

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68026

Other (OTH) AF: 0.0209 AC: 44 AN: 2110

Alfa AF: 0.0144 Hom.: 88

Bravo AF: 0.0310

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.4
DANN	Benign	0.39
PhyloP100		-0.021
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: rs7875953; hg19: chr9-136640122; COSMIC: COSV64079983;