Variant rs11196686 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001272046.2(VWA2):c.2132A>G(p.Gln711Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 1,550,356 control chromosomes in the GnomAD database, including 6,810 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.084 ( 694 hom., cov: 32)

Exomes 𝑓: 0.082 ( 6116 hom. )

Consequence

VWA2
NM_001272046.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.283

Variant links:

Genes affected

VWA2 (HGNC:24709): (von Willebrand factor A domain containing 2) This gene encodes a member of the von Willebrand factor A-like domain protein superfamily. The encoded protein is localized to the extracellular matrix and may serve as a structural component in basement membranes or in anchoring structures on scaffolds of collagen VII or fibrillin. This gene has been linked to type 1A diabetes and is a candidate serological marker for colon cancer. [provided by RefSeq, Jan 2013]

VWA2 links:

AFAP1L2 (HGNC:25901): (actin filament associated protein 1 like 2) Enables SH2 domain binding activity; SH3 domain binding activity; and protein tyrosine kinase activator activity. Involved in several processes, including positive regulation of epidermal growth factor receptor signaling pathway; regulation of gene expression; and regulation of mitotic cell cycle. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

AFAP1L2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026874244).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA2	NM_001272046.2 link	c.2132A>G	p.Gln711Arg	missense_variant	13/14	ENST00000392982.8	NP_001258975.1	Q5GFL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA2	ENST00000392982.8 link	c.2132A>G	p.Gln711Arg	missense_variant	13/14	1	NM_001272046.2	ENSP00000376708.3		Q5GFL6-1

Frequencies

GnomAD3 genomes

AF:

0.0844

AC:

12840

AN:

152078

Hom.:

694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0791

Gnomad AMI

AF:

0.0791

Gnomad AMR

AF:

0.0669

Gnomad ASJ

AF:

0.0893

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.0978

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0687

Gnomad OTH

AF:

0.0788

GnomAD3 exomes

AF:

0.105

AC:

15621

AN:

149036

Hom.:

1127

AF XY:

0.107

AC XY:

8556

AN XY:

80266

show subpopulations

Gnomad AFR exome

AF:

0.0810

Gnomad AMR exome

AF:

0.0750

Gnomad ASJ exome

AF:

0.0879

Gnomad EAS exome

AF:

0.279

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0685

Gnomad OTH exome

AF:

0.0858

GnomAD4 exome

AF:

0.0821

AC:

114828

AN:

1398160

Hom.:

6116

Cov.:

AF XY:

0.0846

AC XY:

58340

AN XY:

689602

show subpopulations

Gnomad4 AFR exome

AF:

0.0764

Gnomad4 AMR exome

AF:

0.0729

Gnomad4 ASJ exome

AF:

0.0915

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0688

Gnomad4 OTH exome

AF:

0.0885

GnomAD4 genome

AF:

0.0843

AC:

12833

AN:

152196

Hom.:

694

Cov.:

AF XY:

0.0884

AC XY:

6580

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0790

Gnomad4 AMR

AF:

0.0667

Gnomad4 ASJ

AF:

0.0893

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.0978

Gnomad4 NFE

AF:

0.0687

Gnomad4 OTH

AF:

0.0789

Alfa

AF:

0.0748

Hom.:

397

Bravo

AF:

0.0810

TwinsUK

AF:

0.0596

AC:

221

ALSPAC

AF:

0.0680

AC:

262

ExAC

AF:

0.0971

AC:

2132

Asia WGS

AF:

0.193

AC:

669

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.20

DANN

Benign

0.61

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.012

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.47

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.030

REVEL

Benign

0.054

Sift

Benign

0.81

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0050

ClinPred

0.0068

GERP RS

1.7

Varity_R

0.032

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over