Variant 10-114248705-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001272046.2(VWA2):c.-9T>A variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,608,136 control chromosomes in the GnomAD database, including 4,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.093 ( 748 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4172 hom. )

Consequence

VWA2
NM_001272046.2 splice_region, 5_prime_UTR

Scores

Splicing: ADA: 0.0005670

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0140

Variant links:

Genes affected

VWA2 (HGNC:24709): (von Willebrand factor A domain containing 2) This gene encodes a member of the von Willebrand factor A-like domain protein superfamily. The encoded protein is localized to the extracellular matrix and may serve as a structural component in basement membranes or in anchoring structures on scaffolds of collagen VII or fibrillin. This gene has been linked to type 1A diabetes and is a candidate serological marker for colon cancer. [provided by RefSeq, Jan 2013]

VWA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-114248705-T-A is Benign according to our data. Variant chr10-114248705-T-A is described in ClinVar as [Benign]. Clinvar id is 3055865.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA2	NM_001272046.2 linkuse as main transcript	c.-9T>A		splice_region_variant, 5_prime_UTR_variant	2/14	ENST00000392982.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA2	ENST00000392982.8 linkuse as main transcript	c.-9T>A	splice_region_variant, 5_prime_UTR_variant	2/14	1	NM_001272046.2	P1	Q5GFL6-1
VWA2	ENST00000603594.2 linkuse as main transcript	c.-791T>A	splice_region_variant, 5_prime_UTR_variant	2/11	2			Q5GFL6-3
VWA2	ENST00000298715.8 linkuse as main transcript	n.242T>A	splice_region_variant, non_coding_transcript_exon_variant	2/12	2

Frequencies

GnomAD3 genomes

AF:

0.0929

AC:

14118

AN:

152030

Hom.:

745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.0627

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.0670

Gnomad SAS

AF:

0.0352

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0797

Gnomad OTH

AF:

0.0726

GnomAD3 exomes

AF:

0.0708

AC:

17811

AN:

251482

Hom.:

748

AF XY:

0.0678

AC XY:

9214

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0556

Gnomad ASJ exome

AF:

0.0481

Gnomad EAS exome

AF:

0.0674

Gnomad SAS exome

AF:

0.0330

Gnomad FIN exome

AF:

0.0867

Gnomad NFE exome

AF:

0.0748

Gnomad OTH exome

AF:

0.0756

GnomAD4 exome

AF:

0.0729

AC:

106197

AN:

1455988

Hom.:

4172

Cov.:

AF XY:

0.0713

AC XY:

51659

AN XY:

724582

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.0558

Gnomad4 ASJ exome

AF:

0.0501

Gnomad4 EAS exome

AF:

0.0666

Gnomad4 SAS exome

AF:

0.0344

Gnomad4 FIN exome

AF:

0.0894

Gnomad4 NFE exome

AF:

0.0746

Gnomad4 OTH exome

AF:

0.0762

GnomAD4 genome

AF:

0.0930

AC:

14153

AN:

152148

Hom.:

748

Cov.:

AF XY:

0.0917

AC XY:

6819

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0628

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.0673

Gnomad4 SAS

AF:

0.0354

Gnomad4 FIN

AF:

0.0809

Gnomad4 NFE

AF:

0.0797

Gnomad4 OTH

AF:

0.0751

Alfa

AF:

0.0763

Hom.:

362

Bravo

AF:

0.0949

EpiCase

AF:

0.0704

EpiControl

AF:

0.0691

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

VWA2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

4.2

Dann

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00057

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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