NM_001134398.2:c.2589+9C>A

Variant names:

• chr9-133768433-G-T
• rs112576600
• NM_001134398.2:c.2589+9C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001134398.2(VAV2):​c.2589+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,611,446 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (2 hom.)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.166
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-133768433-G-T is Benign according to our data. Variant chr9-133768433-G-T is described in ClinVar as [Benign]. Clinvar id is 711027.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 592 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.2589+9C>A		intron_variant	Intron 29 of 29	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.2589+9C>A		intron_variant	Intron 29 of 29	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.2472+9C>A		intron_variant	Intron 26 of 26	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.2559+9C>A		intron_variant	Intron 27 of 27	5		ENSP00000360917.1

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 590 AN: 152060 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00102 AC: 252 AN: 247826 AF XY: 0.000752

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000395 AC: 577 AN: 1459268 Hom.: 2 Cov.: 31 AF XY: 0.000337 AC XY: 245 AN XY: 726030

African (AFR) AF: 0.0154 AC: 516 AN: 33474

American (AMR) AF: 0.000448 AC: 20 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51492

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111630

Other (OTH) AF: 0.000497 AC: 30 AN: 60352

GnomAD4 genome AF: 0.00389 AC: 592 AN: 152178 Hom.: 10 Cov.: 32 AF XY: 0.00363 AC XY: 270 AN XY: 74396

African (AFR) AF: 0.0139 AC: 575 AN: 41512

American (AMR) AF: 0.000785 AC: 12 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67990

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00242 Hom.: 1

Bravo AF: 0.00472

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs112576600; hg19: chr9-136633555;