rs160278

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004385.5(VCAN):c.6902T>A(p.Phe2301Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,613,750 control chromosomes in the GnomAD database, including 188,655 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F2301C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.50 ( 18948 hom., cov: 32)

Exomes 𝑓: 0.48 ( 169707 hom. )

Consequence

VCAN
NM_004385.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.451

Publications

36 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.704877E-5).

BP6

Variant 5-83539905-T-A is Benign according to our data. Variant chr5-83539905-T-A is described in ClinVar as Benign. ClinVar VariationId is 198798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5 link	c.6902T>A	p.Phe2301Tyr	missense_variant	Exon 8 of 15	ENST00000265077.8	NP_004376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8 link	c.6902T>A	p.Phe2301Tyr	missense_variant	Exon 8 of 15	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75648

AN:

151862

Hom.:

18936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.533

GnomAD2 exomes

AF:

0.483

AC:

120998

AN:

250588

AF XY:

0.477

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.496

Gnomad OTH exome

AF:

0.493

GnomAD4 exome

AF:

0.481

AC:

702891

AN:

1461770

Hom.:

169707

Cov.:

AF XY:

0.478

AC XY:

347561

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.498

AC:

16677

AN:

33478

American (AMR)

AF:

0.516

AC:

23059

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

15015

AN:

26132

East Asian (EAS)

AF:

0.463

AC:

18371

AN:

39680

South Asian (SAS)

AF:

0.387

AC:

33351

AN:

86258

European-Finnish (FIN)

AF:

0.507

AC:

27052

AN:

53402

Middle Eastern (MID)

AF:

0.498

AC:

2875

AN:

5768

European-Non Finnish (NFE)

AF:

0.483

AC:

537628

AN:

1111952

Other (OTH)

AF:

0.478

AC:

28863

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

24393

48786

73179

97572

121965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15802

31604

47406

63208

79010

<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:

0.498

AC:

75693

AN:

151980

Hom.:

18948

Cov.:

AF XY:

0.498

AC XY:

36944

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.504

AC:

20899

AN:

41462

American (AMR)

AF:

0.523

AC:

7986

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

2020

AN:

3470

East Asian (EAS)

AF:

0.410

AC:

2114

AN:

5156

South Asian (SAS)

AF:

0.390

AC:

1881

AN:

4818

European-Finnish (FIN)

AF:

0.529

AC:

5578

AN:

10544

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33323

AN:

67960

Other (OTH)

AF:

0.533

AC:

1125

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1980

3959

5939

7918

9898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.476

Hom.:

10114

Bravo

AF:

0.498

TwinsUK

AF:

0.486

AC:

1803

ALSPAC

AF:

0.480

AC:

1849

ESP6500AA

AF:

0.499

AC:

2200

ESP6500EA

AF:

0.493

AC:

4244

ExAC

AF:

0.481

AC:

58364

EpiCase

AF:

0.498

EpiControl

AF:

0.498

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

Jan 13, 2015

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 01, 2020

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

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.081

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.080

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.060

T;T

MetaRNN

Benign

0.000027

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.1

N;.

PhyloP100

0.45

PrimateAI

Benign

0.22

PROVEAN

Benign

0.74

N;N

REVEL

Benign

0.066

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.041

MPC

0.089

ClinPred

0.0085

GERP RS

3.6

Varity_R

0.029

gMVP

0.058

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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