9-133763648-T-A

Variant names:

• chr9-133763648-T-A
• rs509590
• NM_001134398.2:c.*414A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134398.2(VAV2):​c.*414A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VAV2 NM_001134398.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 3 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.*414A>T		3_prime_UTR	Exon 30 of 30	NP_001127870.1
	VAV2	NM_001411028.1		c.*414A>T		3_prime_UTR	Exon 28 of 28	NP_001397957.1
	VAV2	NM_003371.4		c.*414A>T		3_prime_UTR	Exon 27 of 27	NP_003362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV2	ENST00000371850.8	TSL:1 MANE Select	c.*414A>T		3_prime_UTR	Exon 30 of 30	ENSP00000360916.3
	VAV2	ENST00000406606.7	TSL:1	c.*414A>T		3_prime_UTR	Exon 27 of 27	ENSP00000385362.3
	VAV2	ENST00000371851.1	TSL:5	c.*414A>T		3_prime_UTR	Exon 28 of 28	ENSP00000360917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 54936 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28746

African (AFR) AF: 0.00 AC: 0 AN: 1248

American (AMR) AF: 0.00 AC: 0 AN: 3240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1328

East Asian (EAS) AF: 0.00 AC: 0 AN: 2052

South Asian (SAS) AF: 0.00 AC: 0 AN: 7102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 33426

Other (OTH) AF: 0.00 AC: 0 AN: 3190

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.73
PhyloP100		-1.1

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: rs509590; hg19: chr9-136628770;