Variant 10-114278053-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000392982.8(VWA2):c.700+6A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,608,010 control chromosomes in the GnomAD database, including 129 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 0.0070 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 123 hom. )

Consequence

VWA2
ENST00000392982.8 splice_region, intron

Scores

Splicing: ADA: 0.00006753

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.511

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:

VWA2 (HGNC:):

VWA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-114278053-A-C is Benign according to our data. Variant chr10-114278053-A-C is described in ClinVar as [Benign]. Clinvar id is 784517.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA2	NM_001272046.2 linkuse as main transcript	c.700+6A>C		splice_region_variant, intron_variant		ENST00000392982.8	NP_001258975.1	Q5GFL6-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
VWA2	ENST00000392982.8 linkuse as main transcript	c.700+6A>C	splice_region_variant, intron_variant	1	NM_001272046.2	ENSP00000376708.3	Q5GFL6-1
VWA2	ENST00000603594.2 linkuse as main transcript	c.-217+6A>C	splice_region_variant, intron_variant	2		ENSP00000473752.2	Q5GFL6-3
VWA2	ENST00000298715.8 linkuse as main transcript	n.950+6A>C	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00701

AC:

1067

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00962

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00675

AC:

1681

AN:

249140

Hom.:

AF XY:

0.00706

AC XY:

953

AN XY:

134912

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00936

Gnomad FIN exome

AF:

0.00169

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00657

GnomAD4 exome

AF:

0.0110

AC:

15960

AN:

1455720

Hom.:

123

Cov.:

AF XY:

0.0109

AC XY:

7856

AN XY:

722974

show subpopulations

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.00450

Gnomad4 ASJ exome

AF:

0.000422

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.00194

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.00845

GnomAD4 genome

AF:

0.00702

AC:

1069

AN:

152290

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

525

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00808

Hom.:

Bravo

AF:

0.00746

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

VWA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 13, 2022

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.45

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000068

dbscSNV1_RF

Benign

0.0060

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

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