dbSNP rs149309552: VWA2:p.Arg69Met (chr10-114254993-G-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001272046.2(VWA2):c.206G>T(p.Arg69Met) variant causes a missense change. The variant allele was found at a frequency of 0.00227 in 1,613,194 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 5 hom. )

Consequence

VWA2
NM_001272046.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.69

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

congenital anomaly of kidney and urinary tract
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

VWA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022470683).

BP6

Variant 10-114254993-G-T is Benign according to our data. Variant chr10-114254993-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3050813.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272046.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA2	NM_001272046.2	MANE Select	c.206G>T	p.Arg69Met	missense	Exon 4 of 14	NP_001258975.1	Q5GFL6-1
	VWA2	NM_001320804.1		c.206G>T	p.Arg69Met	missense	Exon 4 of 14	NP_001307733.1	Q5GFL6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VWA2	ENST00000392982.8	TSL:1 MANE Select	c.206G>T	p.Arg69Met	missense	Exon 4 of 14	ENSP00000376708.3	Q5GFL6-1
VWA2	ENST00000892505.1		c.206G>T	p.Arg69Met	missense	Exon 4 of 14	ENSP00000562564.1
VWA2	ENST00000942547.1		c.206G>T	p.Arg69Met	missense	Exon 4 of 13	ENSP00000612606.1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

326

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00207

AC:

519

AN:

250676

AF XY:

0.00203

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.000996

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00656

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00228

AC:

3331

AN:

1460934

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

1633

AN XY:

726726

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33478

American (AMR)

AF:

0.00121

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00126

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00641

AC:

338

AN:

52708

Middle Eastern (MID)

AF:

0.00284

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.00248

AC:

2756

AN:

1111938

Other (OTH)

AF:

0.00189

AC:

114

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

202

403

605

806

1008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00214

AC:

326

AN:

152260

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41556

American (AMR)

AF:

0.00327

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00547

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00271

AC:

184

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00174

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00189

AC:

230

EpiCase

AF:

0.00322

EpiControl

AF:

0.00231

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

VWA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Benign

0.037

MetaRNN

Benign

0.022

MetaSVM

Uncertain

0.24

MutationAssessor

Uncertain

2.6

PhyloP100

4.7

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.59

Sift

Benign

0.12

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.71

MVP

0.72

ClinPred

0.049

GERP RS

5.2

Varity_R

0.43

gMVP

0.74

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over