dbSNP rs2070985: DCN:c.-33-701G>C (chr12-91179286-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001920.5(DCN):c.-33-701G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,514 control chromosomes in the GnomAD database, including 1,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1407 hom., cov: 32)

Exomes 𝑓: 0.061 ( 0 hom. )

Consequence

DCN
NM_001920.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.384

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCN	NM_001920.5 link	c.-33-701G>C		intron_variant	Intron 1 of 7	ENST00000052754.10	NP_001911.1	P07585-1Q6FH10
DCN	NM_133503.4 link	c.-34+76G>C		intron_variant	Intron 1 of 7		NP_598010.1	P07585-1Q6FH10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10 link	c.-33-701G>C		intron_variant	Intron 1 of 7	1	NM_001920.5	ENSP00000052754.5		P07585-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17696

AN:

152088

Hom.:

1398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0657

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0688

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.0613

AC:

AN:

310

Hom.:

Cov.:

AF XY:

0.0613

AC XY:

AN XY:

212

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.143

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0519

AC:

AN:

270

Other (OTH)

AF:

0.0833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.117

AC:

17736

AN:

152204

Hom.:

1407

Cov.:

AF XY:

0.114

AC XY:

8447

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.219

AC:

9082

AN:

41504

American (AMR)

AF:

0.105

AC:

1606

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

533

AN:

3470

East Asian (EAS)

AF:

0.139

AC:

718

AN:

5174

South Asian (SAS)

AF:

0.0658

AC:

317

AN:

4820

European-Finnish (FIN)

AF:

0.0441

AC:

468

AN:

10614

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0688

AC:

4677

AN:

68014

Other (OTH)

AF:

0.120

AC:

253

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

772

1543

2315

3086

3858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.0915

Hom.:

143

Bravo

AF:

0.128

Asia WGS

AF:

0.109

AC:

378

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.2

(source)

DANN

Benign

0.50

PhyloP100

0.38

PromoterAI

0.019

Neutral

(source)

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

Computational scores

Splicing

Publications

Other links and lift over