Variant 1-1435798-TGGCGCGGAGC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The ENST00000476993.2(VWA1):c.62_71delGCGCGGAGCG(p.Gly21fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,202,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

VWA1
ENST00000476993.2 frameshift, splice_region

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

VWA1 (HGNC:30910): (von Willebrand factor A domain containing 1) VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

VWA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-1435798-TGGCGCGGAGC-T is Pathogenic according to our data. Variant chr1-1435798-TGGCGCGGAGC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 830324.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-1435798-TGGCGCGGAGC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA1	NM_022834.5 linkuse as main transcript	c.62_71delGCGCGGAGCG	p.Gly21fs	frameshift_variant, splice_region_variant	1/3	ENST00000476993.2	NP_073745.2	Q6PCB0-1
VWA1	NM_199121.3 linkuse as main transcript	c.62_71delGCGCGGAGCG	p.Gly21fs	frameshift_variant, splice_region_variant	1/3		NP_954572.2	Q6PCB0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VWA1	ENST00000476993.2 linkuse as main transcript	c.62_71delGCGCGGAGCG	p.Gly21fs	frameshift_variant, splice_region_variant	1/3	1	NM_022834.5	ENSP00000417185.1	Q6PCB0-1
VWA1	ENST00000471398.1 linkuse as main transcript	c.62_71delGCGCGGAGCG	p.Gly21fs	frameshift_variant, splice_region_variant	1/2	3		ENSP00000464343.1	J3QRR0
VWA1	ENST00000338660.5 linkuse as main transcript	c.62_71delGCGCGGAGCG	p.Gly21fs	frameshift_variant, splice_region_variant	1/3	2		ENSP00000423404.1	Q6PCB0-3
VWA1	ENST00000495558.1 linkuse as main transcript	c.-33+664_-33+673delGCGCGGAGCG		intron_variant		2		ENSP00000463643.1	J3QLP3

Frequencies

GnomAD3 genomes

AF:

0.0000468

AC:

AN:

149504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000418

AC:

AN:

1052794

Hom.:

AF XY:

0.0000489

AC XY:

AN XY:

511400

show subpopulations

Gnomad4 AFR exome

AF:

0.0000499

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000168

Gnomad4 EAS exome

AF:

0.0000715

Gnomad4 SAS exome

AF:

0.000258

Gnomad4 FIN exome

AF:

0.0000549

Gnomad4 NFE exome

AF:

0.0000311

Gnomad4 OTH exome

AF:

0.0000257

GnomAD4 genome

AF:

0.0000468

AC:

AN:

149504

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72886

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000299

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Neuromuscular disease

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Section for Clinical Neurogenetics, University of Tübingen

Jan 01, 2020

- -

Neuronopathy, distal hereditary motor, autosomal recessive 7

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 17, 2023

- -

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