Variant 10-114285935-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001272046.2(VWA2):c.998-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,582,824 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

VWA2
NM_001272046.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003656

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.400

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:

AFAP1L2 (HGNC:):

AFAP1L2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-114285935-G-A is Benign according to our data. Variant chr10-114285935-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 712383.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA2	NM_001272046.2 linkuse as main transcript	c.998-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000392982.8	NP_001258975.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
VWA2	ENST00000392982.8 linkuse as main transcript	c.998-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_001272046.2	ENSP00000376708	P1	Q5GFL6-1
VWA2	ENST00000603594.2 linkuse as main transcript	c.86-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000473752		Q5GFL6-3
VWA2	ENST00000298715.8 linkuse as main transcript	n.1248-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000190

AC:

AN:

232060

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

124468

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000659

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.000528

GnomAD4 exome

AF:

0.000153

AC:

219

AN:

1430536

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

113

AN XY:

706552

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.000830

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000186

GnomAD4 genome

AF:

0.000309

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

VWA2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2019

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.024

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