rs160278

chr5-83539905-T-Achr5-83539905-T-Cchr5-83539905-T-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin 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

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=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 id is 198798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83539905-T-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
VCAN	NM_004385.5 linkuse as main transcript	c.6902T>A	p.Phe2301Tyr	missense_variant	8/15	ENST00000265077.8
VCAN-AS1	NR_136215.1 linkuse as main transcript	n.285-5732A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAN	ENST00000265077.8 linkuse as main transcript	c.6902T>A	p.Phe2301Tyr	missense_variant	8/15	1	NM_004385.5		P13611-1

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

GnomAD3 exomes

AF:

0.483

AC:

120998

AN:

250588

Hom.:

29492

AF XY:

0.477

AC XY:

64561

AN XY:

135448

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 SAS exome

AF:

0.384

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

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.507

Gnomad4 NFE exome

AF:

0.483

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.498

AC:

75693

AN:

151980

Hom.:

18948

Cov.:

AF XY:

0.498

AC XY:

36944

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.504

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.582

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.390

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.490

Gnomad4 OTH

AF:

0.533

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 13, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 01, 2020	- -

Vitreoretinopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

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;.

MutationTaster

Benign

1.0

P;P;P;P;P

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

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