NM_001134398.2:c.204+21854T>C

Variant names:

• chr9-133970221-A-G
• rs3780792
• NM_001134398.2:c.204+21854T>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.204+21854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,068 control chromosomes in the GnomAD database, including 6,887 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 0.29 (6887 hom., cov: 32)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 24 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.204+21854T>C		intron_variant	Intron 1 of 29	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.204+21854T>C		intron_variant	Intron 1 of 29	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.204+21854T>C		intron_variant	Intron 1 of 26	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.204+21854T>C		intron_variant	Intron 1 of 27	5		ENSP00000360917.1
VAV2	ENST00000486113.1	n.185+21854T>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43757 AN: 151950 Hom.: 6886 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.288 AC: 43758 AN: 152068 Hom.: 6887 Cov.: 32 AF XY: 0.292 AC XY: 21715 AN XY: 74338

African (AFR) AF: 0.194 AC: 8042 AN: 41496

American (AMR) AF: 0.243 AC: 3722 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3468

East Asian (EAS) AF: 0.151 AC: 780 AN: 5156

South Asian (SAS) AF: 0.445 AC: 2145 AN: 4822

European-Finnish (FIN) AF: 0.384 AC: 4061 AN: 10576

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22667 AN: 67940

Other (OTH) AF: 0.282 AC: 597 AN: 2114

Alfa AF: 0.317 Hom.: 31055

Bravo AF: 0.269

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.96
DANN	Benign	0.29
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3780792; hg19: chr9-136835343; COSMIC: COSV64081009;