Variant 10-114286037-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001272046.2(VWA2):c.1096G>A(p.Val366Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,614,142 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 10 hom., cov: 33)

Exomes 𝑓: 0.013 ( 144 hom. )

Consequence

VWA2
NM_001272046.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.59

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:):

AFAP1L2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010355711).

BP6

Variant 10-114286037-G-A is Benign according to our data. Variant chr10-114286037-G-A is described in ClinVar as [Benign]. Clinvar id is 774687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA2	NM_001272046.2 linkuse as main transcript	c.1096G>A	p.Val366Met	missense_variant	11/14	ENST00000392982.8	NP_001258975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA2	ENST00000392982.8 linkuse as main transcript	c.1096G>A	p.Val366Met	missense_variant	11/14	1	NM_001272046.2	ENSP00000376708	P1	Q5GFL6-1
VWA2	ENST00000603594.2 linkuse as main transcript	c.184G>A	p.Val62Met	missense_variant	10/11	2		ENSP00000473752		Q5GFL6-3
VWA2	ENST00000298715.8 linkuse as main transcript	n.1346G>A		non_coding_transcript_exon_variant	11/12	2

Frequencies

GnomAD3 genomes

AF:

0.00922

AC:

1404

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.0101

AC:

2530

AN:

251214

Hom.:

AF XY:

0.0101

AC XY:

1377

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00332

Gnomad AMR exome

AF:

0.00630

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00382

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0126

AC:

18437

AN:

1461792

Hom.:

144

Cov.:

AF XY:

0.0123

AC XY:

8949

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00715

Gnomad4 ASJ exome

AF:

0.0195

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00371

Gnomad4 FIN exome

AF:

0.0195

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.00922

AC:

1405

AN:

152350

Hom.:

Cov.:

AF XY:

0.00948

AC XY:

706

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00264

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.0227

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00836

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.00934

AC:

1134

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0156

EpiControl

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

-0.085

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

0.84

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.39

N;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.018

D;.

Sift4G

Uncertain

0.045

D;D

Polyphen

0.99

D;P

Vest4

0.40

MPC

0.55

ClinPred

0.024

GERP RS

2.7

Varity_R

0.066

gMVP

0.59

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over