Variant rs10622288 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000552.5(VWF):c.1946-15_1946-14insTCT variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -1.20

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
VWF	NM_000552.5 linkuse as main transcript	c.1946-15_1946-14insTCT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261405.10
VWF	XM_047429501.1 linkuse as main transcript	c.1946-15_1946-14insTCT		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10 linkuse as main transcript	c.1946-15_1946-14insTCT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000552.5	P1	P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.420+57717_420+57718insTCT		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes

AF:

0.841

AC:

202052

AN:

240314

Hom.:

85059

AF XY:

0.838

AC XY:

109155

AN XY:

130200

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 SAS exome

AF:

0.811

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

Gnomad4 AFR exome

AF:

0.870

Gnomad4 AMR exome

AF:

0.861

Gnomad4 ASJ exome

AF:

0.857

Gnomad4 EAS exome

AF:

0.765

Gnomad4 SAS exome

AF:

0.806

Gnomad4 FIN exome

AF:

0.822

Gnomad4 NFE exome

AF:

0.855

Gnomad4 OTH exome

AF:

0.849

GnomAD4 genome

AF:

0.852

AC:

129455

AN:

151948

Hom.:

55266

Cov.:

AF XY:

0.852

AC XY:

63236

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.866

Gnomad4 AMR

AF:

0.874

Gnomad4 ASJ

AF:

0.858

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.821

Gnomad4 FIN

AF:

0.826

Gnomad4 NFE

AF:

0.850

Gnomad4 OTH

AF:

0.864

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 25, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

von Willebrand disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

von Willebrand disease type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

von Willebrand disease type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Hereditary von Willebrand disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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