Variant rs7441 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001920.5(DCN):c.*160C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 630,010 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 945 hom., cov: 32)

Exomes 𝑓: 0.070 ( 1349 hom. )

Consequence

DCN
NM_001920.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.52

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 12-91145898-G-A is Benign according to our data. Variant chr12-91145898-G-A is described in ClinVar as [Benign]. Clinvar id is 310647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-91145898-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCN	NM_001920.5 link	c.*160C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000052754.10	NP_001911.1	P07585-1Q6FH10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754 link	c.*160C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001920.5	ENSP00000052754.5		P07585-1

Frequencies

GnomAD3 genomes

AF:

0.0966

AC:

14689

AN:

152080

Hom.:

943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.0745

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.0551

Gnomad SAS

AF:

0.0409

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0680

Gnomad OTH

AF:

0.0963

GnomAD4 exome

AF:

0.0702

AC:

33522

AN:

477812

Hom.:

1349

Cov.:

AF XY:

0.0687

AC XY:

17495

AN XY:

254694

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.0565

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.0575

Gnomad4 SAS exome

AF:

0.0441

Gnomad4 FIN exome

AF:

0.0460

Gnomad4 NFE exome

AF:

0.0699

Gnomad4 OTH exome

AF:

0.0790

GnomAD4 genome

AF:

0.0967

AC:

14711

AN:

152198

Hom.:

945

Cov.:

AF XY:

0.0935

AC XY:

6959

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.0744

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.0550

Gnomad4 SAS

AF:

0.0405

Gnomad4 FIN

AF:

0.0439

Gnomad4 NFE

AF:

0.0680

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0696

Hom.:

329

Bravo

AF:

0.103

Asia WGS

AF:

0.0550

AC:

192

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

-0.34

CADD

Benign

DANN

Benign

0.86

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