5-83541812-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004385.5(VCAN):c.8809G>T(p.Asp2937Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,613,674 control chromosomes in the GnomAD database, including 117,940 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11583 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106357 hom. )

Consequence

VCAN
NM_004385.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.658

Variant links:

Genes affected

VCAN (HGNC:2464): (versican) This gene is a member of the aggrecan/versican proteoglycan family. The protein encoded is a large chondroitin sulfate proteoglycan and is a major component of the extracellular matrix. This protein is involved in cell adhesion, proliferation, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Mutations in this gene are the cause of Wagner syndrome type 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

VCAN links:

VCAN-AS1 (HGNC:40163): (VCAN antisense RNA 1)

VCAN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.621314E-4).

BP6

Variant 5-83541812-G-T is Benign according to our data. Variant chr5-83541812-G-T is described in ClinVar as [Benign]. Clinvar id is 198802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83541812-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5 link	c.8809G>T	p.Asp2937Tyr	missense_variant	Exon 8 of 15	ENST00000265077.8	NP_004376.2	P13611-1A0A024RAQ9Q59FG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8 link	c.8809G>T	p.Asp2937Tyr	missense_variant	Exon 8 of 15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58803

AN:

151792

Hom.:

11575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.479

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.419

GnomAD3 exomes

AF:

0.385

AC:

96445

AN:

250812

Hom.:

18860

AF XY:

0.378

AC XY:

51249

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.343

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.379

AC:

554703

AN:

1461764

Hom.:

106357

Cov.:

AF XY:

0.376

AC XY:

273768

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.364

Gnomad4 AMR exome

AF:

0.453

Gnomad4 ASJ exome

AF:

0.477

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.388

Gnomad4 NFE exome

AF:

0.381

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.387

AC:

58832

AN:

151910

Hom.:

11583

Cov.:

AF XY:

0.385

AC XY:

28603

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.371

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.479

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.388

Hom.:

28908

Bravo

AF:

0.391

TwinsUK

AF:

0.389

AC:

1443

ALSPAC

AF:

0.378

AC:

1456

ESP6500AA

AF:

0.369

AC:

1625

ESP6500EA

AF:

0.399

AC:

3433

ExAC

AF:

0.381

AC:

46242

Asia WGS

AF:

0.286

AC:

992

AN:

3478

EpiCase

AF:

0.399

EpiControl

AF:

0.398

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wagner syndrome

Benign:3

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

May 08, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Sep 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19655167) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Vitreoretinopathy

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.00056

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.094

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

0.98

D;D

Vest4

0.032

MPC

0.27

ClinPred

0.028

GERP RS

0.82

Varity_R

0.068

gMVP

0.18

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