Variant 7-49775818-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198570.5(VWC2):c.383A>G(p.Gln128Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000339 in 1,542,826 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

VWC2
NM_198570.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

Variant links:

Genes affected

VWC2 (HGNC:30200): (von Willebrand factor C domain containing 2) This gene encodes a secreted bone morphogenic protein antagonist. The encoded protein is possibly involved in neural function and development and may have a role in cell adhesion.[provided by RefSeq, Oct 2009]

VWC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032797337).

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWC2	NM_198570.5 linkuse as main transcript	c.383A>G	p.Gln128Arg	missense_variant	2/4	ENST00000340652.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWC2	ENST00000340652.5 linkuse as main transcript	c.383A>G	p.Gln128Arg	missense_variant	2/4	1	NM_198570.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000277

AC:

AN:

137014

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

74532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000410

Gnomad ASJ exome

AF:

0.000625

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.000571

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000344

AC:

479

AN:

1390522

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

262

AN XY:

685386

show subpopulations

Gnomad4 AFR exome

AF:

0.0000642

Gnomad4 AMR exome

AF:

0.0000561

Gnomad4 ASJ exome

AF:

0.000680

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000305

Gnomad4 FIN exome

AF:

0.000734

Gnomad4 NFE exome

AF:

0.000344

Gnomad4 OTH exome

AF:

0.000520

GnomAD4 genome

AF:

0.000289

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000537

Hom.:

Bravo

AF:

0.000302

ExAC

AF:

0.0000692

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

May 11, 2022

The c.383A>G (p.Q128R) alteration is located in exon 2 (coding exon 1) of the VWC2 gene. This alteration results from a A to G substitution at nucleotide position 383, causing the glutamine (Q) at amino acid position 128 to be replaced by an arginine (R). 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

0.070

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.039

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.46

M_CAP

Benign

0.074

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.94

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

REVEL

Benign

0.057

Sift

Benign

0.092

Sift4G

Benign

0.22

Polyphen

0.031

Vest4

0.21

MutPred

0.22

Gain of methylation at Q128 (P = 0.0336);

MVP

0.082

MPC

1.1

ClinPred

0.040

GERP RS

4.0

Varity_R

0.16

gMVP

0.41

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