rs2548541

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004385.5(VCAN):c.4323G>A(p.Gln1441Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,613,732 control chromosomes in the GnomAD database, including 315,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35430 hom., cov: 32)

Exomes 𝑓: 0.62 ( 280193 hom. )

Consequence

VCAN
NM_004385.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.634

Publications

22 publications found

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 5-83537326-G-A is Benign according to our data. Variant chr5-83537326-G-A is described in ClinVar as Benign. ClinVar VariationId is 198803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.634 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5 link	c.4323G>A	p.Gln1441Gln	synonymous_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.4323G>A	p.Gln1441Gln	synonymous_variant	Exon 8 of 15	1	NM_004385.5	ENSP00000265077.3		P13611-1

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102774

AN:

151908

Hom.:

35382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.669

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.698

GnomAD2 exomes

AF:

0.643

AC:

161062

AN:

250626

AF XY:

0.644

show subpopulations

Gnomad AFR exome

AF:

0.808

Gnomad AMR exome

AF:

0.589

Gnomad ASJ exome

AF:

0.715

Gnomad EAS exome

AF:

0.629

Gnomad FIN exome

AF:

0.654

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.617

AC:

902380

AN:

1461702

Hom.:

280193

Cov.:

AF XY:

0.620

AC XY:

450726

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.813

AC:

27196

AN:

33466

American (AMR)

AF:

0.594

AC:

26521

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

18570

AN:

26130

East Asian (EAS)

AF:

0.658

AC:

26127

AN:

39696

South Asian (SAS)

AF:

0.702

AC:

60573

AN:

86258

European-Finnish (FIN)

AF:

0.648

AC:

34601

AN:

53402

Middle Eastern (MID)

AF:

0.699

AC:

4030

AN:

5768

European-Non Finnish (NFE)

AF:

0.599

AC:

666428

AN:

1111924

Other (OTH)

AF:

0.635

AC:

38334

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

25055

50111

75166

100222

125277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18220

36440

54660

72880

91100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.677

AC:

102877

AN:

152030

Hom.:

35430

Cov.:

AF XY:

0.681

AC XY:

50569

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.805

AC:

33410

AN:

41492

American (AMR)

AF:

0.623

AC:

9506

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

2468

AN:

3466

East Asian (EAS)

AF:

0.635

AC:

3274

AN:

5156

South Asian (SAS)

AF:

0.719

AC:

3462

AN:

4818

European-Finnish (FIN)

AF:

0.669

AC:

7066

AN:

10568

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.609

AC:

41355

AN:

67958

Other (OTH)

AF:

0.698

AC:

1473

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1642

3285

4927

6570

8212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.636

Hom.:

51514

Bravo

AF:

0.674

Asia WGS

AF:

0.663

AC:

2303

AN:

3478

EpiCase

AF:

0.622

EpiControl

AF:

0.623

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 08, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Vitreoretinopathy

Benign:1

Jan 13, 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

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.14

(source)

DANN

Benign

0.81

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over