9-133772055-A-ACACACGGCCCCGGCGGTCACTGCGTGAGGGC

Position:

• chr9-133772055-A-ACACACGGCCCCGGCGGTCACTGCGTGAGGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001134398.2(VAV2):​c.2136-10_2136-9insGCCCTCACGCAGTGACCGCCGGGGCCGTGTG variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,448,216 control chromosomes in the GnomAD database, including 115,689 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9887 hom., cov: 37)
  • Exomes 𝑓: 0.39 (115689 hom.)
  • Failed GnomAD Quality Control
• Consequence: VAV2 NM_001134398.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-133772055-A-ACACACGGCCCCGGCGGTCACTGCGTGAGGGC is Benign according to our data. Variant chr9-133772055-A-ACACACGGCCCCGGCGGTCACTGCGTGAGGGC is described in ClinVar as [Benign]. Clinvar id is 768335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV2	NM_001134398.2	c.2136-10_2136-9insGCCCTCACGCAGTGACCGCCGGGGCCGTGTG		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371850.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV2	ENST00000371850.8	c.2136-10_2136-9insGCCCTCACGCAGTGACCGCCGGGGCCGTGTG		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001134398.2	A1
VAV2	ENST00000406606.7	c.2106-10_2106-9insGCCCTCACGCAGTGACCGCCGGGGCCGTGTG		splice_polypyrimidine_tract_variant, intron_variant		1		P4
VAV2	ENST00000371851.1	c.2106-10_2106-9insGCCCTCACGCAGTGACCGCCGGGGCCGTGTG		splice_polypyrimidine_tract_variant, intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53331 AN: 151270 Hom.: 9878 Cov.: 37

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.387 AC: 560596 AN: 1448216 Hom.: 115689 Cov.: 32 AF XY: 0.388 AC XY: 279975 AN XY: 720980

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.0241

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.353 AC: 53370 AN: 151390 Hom.: 9887 Cov.: 37 AF XY: 0.347 AC XY: 25670 AN XY: 73978

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.0428

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.354

Alfa AF: 0.208 Hom.: 1088

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554768759; hg19: chr9-136637177;