rs3138268

Variant names:

Variant summary

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

The NM_001920.5(DCN):c.803C>T(p.Thr268Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,614,014 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 62 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 67 hom. )

Consequence

DCN
NM_001920.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.05

Publications

8 publications found

Variant links:

Genes affected

DCN (HGNC:2705): (decorin) This gene encodes a member of the small leucine-rich proteoglycan family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. This protein plays a role in collagen fibril assembly. Binding of this protein to multiple cell surface receptors mediates its role in tumor suppression, including a stimulatory effect on autophagy and inflammation and an inhibitory effect on angiogenesis and tumorigenesis. This gene and the related gene biglycan are thought to be the result of a gene duplication. Mutations in this gene are associated with congenital stromal corneal dystrophy in human patients. [provided by RefSeq, Nov 2015]

DCN Gene-Disease associations (from GenCC):

congenital stromal corneal dystrophy
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

DCN 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=0.0016803145).

BP6

Variant 12-91151736-G-A is Benign according to our data. Variant chr12-91151736-G-A is described in ClinVar as Benign. ClinVar VariationId is 310656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001920.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DCN	NM_001920.5	MANE Select	c.803C>T	p.Thr268Met	missense	Exon 7 of 8	NP_001911.1
DCN	NM_133503.4		c.803C>T	p.Thr268Met	missense	Exon 7 of 8	NP_598010.1
DCN	NM_133504.3		c.476C>T	p.Thr159Met	missense	Exon 4 of 5	NP_598011.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DCN	ENST00000052754.10	TSL:1 MANE Select	c.803C>T	p.Thr268Met	missense	Exon 7 of 8	ENSP00000052754.5
DCN	ENST00000420120.6	TSL:1	c.476C>T	p.Thr159Met	missense	Exon 4 of 5	ENSP00000413723.2
DCN	ENST00000425043.5	TSL:1	c.362C>T	p.Thr121Met	missense	Exon 3 of 4	ENSP00000401021.1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2461

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00477

AC:

1199

AN:

251402

AF XY:

0.00387

show subpopulations

Gnomad AFR exome

AF:

0.0593

Gnomad AMR exome

AF:

0.00466

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00193

AC:

2827

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1275

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.0593

AC:

1986

AN:

33468

American (AMR)

AF:

0.00519

AC:

232

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.000162

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00937

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000228

AC:

253

AN:

1111910

Other (OTH)

AF:

0.00470

AC:

284

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

140

280

421

561

701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.0162

AC:

2465

AN:

152258

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1165

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0554

AC:

2300

AN:

41516

American (AMR)

AF:

0.00738

AC:

113

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68028

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

118

236

354

472

590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00658

Hom.:

Bravo

AF:

0.0190

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0533

AC:

235

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00563

AC:

684

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital stromal corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.15

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.44

PhyloP100

1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

0.55

REVEL

Benign

0.047

Sift

Benign

0.22

Sift4G

Benign

0.11

Polyphen

0.084

Vest4

0.14

MVP

0.38

MPC

0.25

ClinPred

0.0061

GERP RS

1.7

Varity_R

0.021

gMVP

0.49

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over