rs2239160

Variant names:

• chr12-6053588-A-G
• rs2239160
• NM_000552.5:c.1946-805T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-6053588-A-G
• chr12-6053588-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000552.5(VWF):​c.1946-805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,168 control chromosomes in the GnomAD database, including 58,147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (58147 hom., cov: 31)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.1946-805T>C		intron_variant	Intron 15 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.1946-805T>C		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	c.1946-805T>C		intron_variant	Intron 15 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.420+56927T>C		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132782 AN: 152048 Hom.: 58119 Cov.: 31

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.899

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.873 AC: 132859 AN: 152168 Hom.: 58147 Cov.: 31 AF XY: 0.873 AC XY: 64920 AN XY: 74380

African (AFR) AF: 0.853 AC: 35381 AN: 41496

American (AMR) AF: 0.897 AC: 13725 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3191 AN: 3466

East Asian (EAS) AF: 0.781 AC: 4040 AN: 5174

South Asian (SAS) AF: 0.866 AC: 4171 AN: 4816

European-Finnish (FIN) AF: 0.856 AC: 9071 AN: 10592

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60289 AN: 68006

Other (OTH) AF: 0.895 AC: 1893 AN: 2116

Alfa AF: 0.872 Hom.: 18693

Bravo AF: 0.876

Asia WGS AF: 0.826 AC: 2875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2239160; hg19: chr12-6162754;