Variant chr3-184233393-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001390846.1(VWA5B2):c.526G>A(p.Asp176Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000058 in 1,533,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

VWA5B2
NM_001390846.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.49

Variant links:

Genes affected

VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

VWA5B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05199644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA5B2	NM_001390846.1 linkuse as main transcript	c.526G>A	p.Asp176Asn	missense_variant	4/20	ENST00000691901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
VWA5B2	ENST00000691901.1 linkuse as main transcript	c.526G>A	p.Asp176Asn	missense_variant	4/20		NM_001390846.1	P1
VWA5B2	ENST00000426955.6 linkuse as main transcript	c.526G>A	p.Asp176Asn	missense_variant	3/19	1		P1
VWA5B2	ENST00000497229.1 linkuse as main transcript	n.794G>A		non_coding_transcript_exon_variant	1/3	2
VWA5B2	ENST00000273794.5 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000161

AC:

AN:

130368

Hom.:

AF XY:

0.000130

AC XY:

AN XY:

69420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000570

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000462

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000478

AC:

AN:

1381600

Hom.:

Cov.:

AF XY:

0.0000558

AC XY:

AN XY:

680756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.000367

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000405

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.000151

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000242

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.526G>A (p.D176N) alteration is located in exon 3 (coding exon 3) of the VWA5B2 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the aspartic acid (D) at amino acid position 176 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0067

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

M_CAP

Benign

0.016

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.58

REVEL

Benign

0.12

Sift

Benign

0.18

Sift4G

Benign

0.23

Vest4

0.34

MutPred

0.22

Loss of glycosylation at S177 (P = 0.0585);

MVP

0.55

MPC

1.6

ClinPred

0.13

GERP RS

4.2

Varity_R

0.10

gMVP

0.52

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

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