rs10622288

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000552.5(VWF):c.1946-17_1946-15dupTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,609,740 control chromosomes in the GnomAD database, including 580,553 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55266 hom., cov: 0)

Exomes 𝑓: 0.85 ( 525287 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -1.20

Publications

5 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 -16 ACMG points.

BP6

Variant 12-6052797-G-GAGA is Benign according to our data. Variant chr12-6052797-G-GAGA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.1946-17_1946-15dupTCT		intron_variant	Intron 15 of 51	ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 link	c.1946-17_1946-15dupTCT		intron_variant	Intron 15 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.1946-15_1946-14insTCT		intron_variant	Intron 15 of 51	1	NM_000552.5	ENSP00000261405.5		P04275-1
VWF	ENST00000538635.5 link	n.420+57717_420+57718insTCT		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129367

AN:

151828

Hom.:

55230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.867

Gnomad AMI

AF:

0.809

Gnomad AMR

AF:

0.874

Gnomad ASJ

AF:

0.858

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.821

Gnomad FIN

AF:

0.826

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.850

Gnomad OTH

AF:

0.869

GnomAD2 exomes

AF:

0.841

AC:

202052

AN:

240314

AF XY:

0.838

show subpopulations

Gnomad AFR exome

AF:

0.870

Gnomad AMR exome

AF:

0.864

Gnomad ASJ exome

AF:

0.856

Gnomad EAS exome

AF:

0.785

Gnomad FIN exome

AF:

0.827

Gnomad NFE exome

AF:

0.848

Gnomad OTH exome

AF:

0.848

GnomAD4 exome

AF:

0.848

AC:

1236714

AN:

1457792

Hom.:

525287

Cov.:

AF XY:

0.846

AC XY:

613360

AN XY:

724874

show subpopulations

African (AFR)

AF:

0.870

AC:

29053

AN:

33388

American (AMR)

AF:

0.861

AC:

37924

AN:

44026

Ashkenazi Jewish (ASJ)

AF:

0.857

AC:

22324

AN:

26046

East Asian (EAS)

AF:

0.765

AC:

30237

AN:

39536

South Asian (SAS)

AF:

0.806

AC:

69093

AN:

85772

European-Finnish (FIN)

AF:

0.822

AC:

43577

AN:

52994

Middle Eastern (MID)

AF:

0.843

AC:

4859

AN:

5762

European-Non Finnish (NFE)

AF:

0.855

AC:

948527

AN:

1110034

Other (OTH)

AF:

0.849

AC:

51120

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10788

21577

32365

43154

53942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21180

42360

63540

84720

105900

<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:

0.852

AC:

129455

AN:

151948

Hom.:

55266

Cov.:

AF XY:

0.852

AC XY:

63236

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.866

AC:

35896

AN:

41430

American (AMR)

AF:

0.874

AC:

13366

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

2979

AN:

3472

East Asian (EAS)

AF:

0.777

AC:

4010

AN:

5162

South Asian (SAS)

AF:

0.821

AC:

3953

AN:

4814

European-Finnish (FIN)

AF:

0.826

AC:

8702

AN:

10532

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.850

AC:

57737

AN:

67938

Other (OTH)

AF:

0.864

AC:

1820

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1000

2001

3001

4002

5002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.826

Hom.:

8617

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

- -

Jan 25, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: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

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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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