dbSNP rs741212: DCN:c.-34+1690T>C (chr12-91180965-A-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.-34+1690T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,250 control chromosomes in the GnomAD database, including 727 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 0.083 ( 727 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

DCN
NM_001920.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.463

Publications

6 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:

ENSG00000293802 (HGNC:):

ENSG00000293802 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCN	NM_001920.5 link	c.-34+1690T>C		intron_variant	Intron 1 of 7	ENST00000052754.10	NP_001911.1	P07585-1Q6FH10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10 link	c.-34+1690T>C		intron_variant	Intron 1 of 7	1	NM_001920.5	ENSP00000052754.5		P07585-1

Frequencies

GnomAD3 genomes

AF:

0.0830

AC:

12621

AN:

152132

Hom.:

728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0464

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.109

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0829

AC:

12614

AN:

152250

Hom.:

727

Cov.:

AF XY:

0.0803

AC XY:

5976

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0210

AC:

874

AN:

41574

American (AMR)

AF:

0.114

AC:

1738

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

469

AN:

3462

East Asian (EAS)

AF:

0.00154

AC:

AN:

5188

South Asian (SAS)

AF:

0.0298

AC:

144

AN:

4826

European-Finnish (FIN)

AF:

0.0464

AC:

492

AN:

10608

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8580

AN:

67994

Other (OTH)

AF:

0.108

AC:

228

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

586

1172

1759

2345

2931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.110

Hom.:

567

Bravo

AF:

0.0852

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.2

(source)

DANN

Benign

0.82

PhyloP100

0.46

PromoterAI

0.0048

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over