rs1803343

chr12-91146007-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.269

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	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	c.*51A>G		3_prime_UTR_variant	8/8	1	NM_001920.5	P1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3173 AN: 152198 Hom.: 81 Cov.: 32

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

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.: 18 AF XY: 0.0226 AC XY: 14297 AN XY: 633988

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.: 82 Cov.: 32 AF XY: 0.0212 AC XY: 1578 AN XY: 74482

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.: 61

Bravo AF: 0.0242

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Other links and lift over

dbSNP: rs1803343; hg19: chr12-91539784;