NM_001134398.2:c.450-1742T>C

Variant names:

• chr9-133813958-A-G
• rs756777
• NM_001134398.2:c.450-1742T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134398.2(VAV2):​c.450-1742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,192 control chromosomes in the GnomAD database, including 6,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6745 hom., cov: 33)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV2	NM_001134398.2	MANE Select	c.450-1742T>C		intron	N/A	NP_001127870.1
	VAV2	NM_001411028.1		c.450-1742T>C		intron	N/A	NP_001397957.1
	VAV2	NM_003371.4		c.450-1742T>C		intron	N/A	NP_003362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV2	ENST00000371850.8	TSL:1 MANE Select	c.450-1742T>C		intron	N/A	ENSP00000360916.3
	VAV2	ENST00000406606.7	TSL:1	c.450-1742T>C		intron	N/A	ENSP00000385362.3
	VAV2	ENST00000371851.1	TSL:5	c.450-1742T>C		intron	N/A	ENSP00000360917.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42257 AN: 152074 Hom.: 6729 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42320 AN: 152192 Hom.: 6745 Cov.: 33 AF XY: 0.276 AC XY: 20532 AN XY: 74414

African (AFR) AF: 0.443 AC: 18403 AN: 41498

American (AMR) AF: 0.282 AC: 4314 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3472

East Asian (EAS) AF: 0.0777 AC: 403 AN: 5184

South Asian (SAS) AF: 0.240 AC: 1160 AN: 4830

European-Finnish (FIN) AF: 0.215 AC: 2281 AN: 10598

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14227 AN: 67992

Other (OTH) AF: 0.243 AC: 514 AN: 2114

Alfa AF: 0.265 Hom.: 5834

Bravo AF: 0.290

Asia WGS AF: 0.195 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.16
PhyloP100		-3.5
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: rs756777; hg19: chr9-136679080;