Variant 12-91146007-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001920.5(DCN):c.*51A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,404,532 control chromosomes in the GnomAD database, including 567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 82 hom., cov: 32)

Exomes 𝑓: 0.023 ( 485 hom. )

Consequence

DCN
NM_001920.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.269

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 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 (BayesDel_noAF=-0.63).

BP6

Variant 12-91146007-T-C is Benign according to our data. Variant chr12-91146007-T-C is described in ClinVar as [Benign]. Clinvar id is 310650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCN	NM_001920.5 linkuse as main transcript	c.*51A>G		3_prime_UTR_variant	8/8	ENST00000052754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCN	ENST00000052754.10 linkuse as main transcript	c.*51A>G		3_prime_UTR_variant	8/8	1	NM_001920.5	P1	P07585-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3173

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00707

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0671

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.0194

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0237

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0263

AC:

6561

AN:

249768

Hom.:

194

AF XY:

0.0244

AC XY:

3297

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.00567

Gnomad AMR exome

AF:

0.0878

Gnomad ASJ exome

AF:

0.00993

Gnomad EAS exome

AF:

0.000657

Gnomad SAS exome

AF:

0.0199

Gnomad FIN exome

AF:

0.00648

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0226

AC:

28338

AN:

1252216

Hom.:

485

Cov.:

AF XY:

0.0226

AC XY:

14297

AN XY:

633988

show subpopulations

Gnomad4 AFR exome

AF:

0.00638

Gnomad4 AMR exome

AF:

0.0851

Gnomad4 ASJ exome

AF:

0.00998

Gnomad4 EAS exome

AF:

0.000491

Gnomad4 SAS exome

AF:

0.0206

Gnomad4 FIN exome

AF:

0.00717

Gnomad4 NFE exome

AF:

0.0228

Gnomad4 OTH exome

AF:

0.0187

GnomAD4 genome

AF:

0.0209

AC:

3180

AN:

152316

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1578

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00707

Gnomad4 AMR

AF:

0.0676

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.0190

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.0237

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0227

Hom.:

Bravo

AF:

0.0242

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital stromal corneal dystrophy

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

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.5

DANN

Benign

0.88

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