rs546732699

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000552.5(VWF):c.3486A>G(p.Pro1162Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 525 hom., cov: 10)

Exomes 𝑓: 0.0082 ( 276 hom. )

Failed GnomAD Quality Control

Consequence

VWF
NM_000552.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.66

Publications

1 publications found

Variant links:

Genes affected

VWF (HGNC:12726): (von Willebrand factor) This gene encodes a glycoprotein involved in hemostasis. The encoded preproprotein is proteolytically processed following assembly into large multimeric complexes. These complexes function in the adhesion of platelets to sites of vascular injury and the transport of various proteins in the blood. Mutations in this gene result in von Willebrand disease, an inherited bleeding disorder. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Oct 2015]

VWF Gene-Disease associations (from GenCC):

hereditary von Willebrand disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
von Willebrand disease type 2B
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
von Willebrand disease 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
von Willebrand disease 1
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
von Willebrand disease type 2A
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
von Willebrand disease type 2M
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
von Willebrand disease 3
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
von Willebrand disease type 2N
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

VWF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 12-6022792-T-C is Benign according to our data. Variant chr12-6022792-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.3486A>G	p.Pro1162Pro	synonymous_variant	Exon 26 of 52	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1 link	c.3486A>G	p.Pro1162Pro	synonymous_variant	Exon 26 of 52		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.3486A>G	p.Pro1162Pro	synonymous_variant	Exon 26 of 52	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5 link	n.421-28858A>G		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.0542

AC:

4843

AN:

89306

Hom.:

523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.0178

Gnomad AMR

AF:

0.0302

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000540

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0185

Gnomad NFE

AF:

0.000962

Gnomad OTH

AF:

0.0650

GnomAD2 exomes

AF:

0.0256

AC:

1391

AN:

54270

AF XY:

0.0228

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00990

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00825

AC:

3624

AN:

439440

Hom.:

276

Cov.:

AF XY:

0.00702

AC XY:

1628

AN XY:

231798

show subpopulations

African (AFR)

AF:

0.209

AC:

2565

AN:

12290

American (AMR)

AF:

0.0184

AC:

346

AN:

18768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13460

East Asian (EAS)

AF:

0.000101

AC:

AN:

29760

South Asian (SAS)

AF:

0.000489

AC:

AN:

44970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27508

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

1926

European-Non Finnish (NFE)

AF:

0.000897

AC:

238

AN:

265318

Other (OTH)

AF:

0.0165

AC:

419

AN:

25440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

157

314

472

629

786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0543

AC:

4855

AN:

89346

Hom.:

525

Cov.:

AF XY:

0.0545

AC XY:

2159

AN XY:

39602

show subpopulations

African (AFR)

AF:

0.208

AC:

4509

AN:

21678

American (AMR)

AF:

0.0300

AC:

213

AN:

7092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2502

East Asian (EAS)

AF:

0.000541

AC:

AN:

3694

South Asian (SAS)

AF:

0.00

AC:

AN:

2142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4480

Middle Eastern (MID)

AF:

0.0164

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.000962

AC:

AN:

45738

Other (OTH)

AF:

0.0644

AC:

AN:

1102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

187

375

562

750

937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0865

Hom.:

Bravo

AF:

0.0730

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

von Willebrand disease type 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

von Willebrand disease type 3

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

von Willebrand disease type 1

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary von Willebrand disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

-0.94

CADD

Benign

0.11

(source)

DANN

Benign

0.41

PhyloP100

-2.7

Mutation Taster

=67/33

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over