rs1803343

Variant names:

• chr12-91146007-T-C
• rs1803343
• ENST00000393155.6:n.*784A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000393155.6(DCN):​n.*784A>G variant causes a non coding transcript exon 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 ENST00000393155.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.269
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393155.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	NM_001920.5	MANE Select	c.*51A>G		3_prime_UTR	Exon 8 of 8	NP_001911.1
	DCN	NM_133503.4		c.*51A>G		3_prime_UTR	Exon 8 of 8	NP_598010.1
	DCN	NM_133504.3		c.*51A>G		3_prime_UTR	Exon 5 of 5	NP_598011.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	ENST00000393155.6	TSL:1	n.*784A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000376862.2
	DCN	ENST00000052754.10	TSL:1 MANE Select	c.*51A>G		3_prime_UTR	Exon 8 of 8	ENSP00000052754.5
	DCN	ENST00000425043.5	TSL:1	c.*51A>G		3_prime_UTR	Exon 4 of 4	ENSP00000401021.1

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

GnomAD2 exomes AF: 0.0263 AC: 6561 AN: 249768 AF XY: 0.0244

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 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

African (AFR) AF: 0.00638 AC: 186 AN: 29162

American (AMR) AF: 0.0851 AC: 3778 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00998 AC: 248 AN: 24858

East Asian (EAS) AF: 0.000491 AC: 19 AN: 38688

South Asian (SAS) AF: 0.0206 AC: 1684 AN: 81852

European-Finnish (FIN) AF: 0.00717 AC: 382 AN: 53284

Middle Eastern (MID) AF: 0.0139 AC: 75 AN: 5396

European-Non Finnish (NFE) AF: 0.0228 AC: 20959 AN: 920898

Other (OTH) AF: 0.0187 AC: 1007 AN: 53708

GnomAD4 genome AF: 0.0209 AC: 3180 AN: 152316 Hom.: 82 Cov.: 32 AF XY: 0.0212 AC XY: 1578 AN XY: 74482

African (AFR) AF: 0.00707 AC: 294 AN: 41562

American (AMR) AF: 0.0676 AC: 1035 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0190 AC: 92 AN: 4830

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1611 AN: 68024

Other (OTH) AF: 0.0180 AC: 38 AN: 2116

Alfa AF: 0.0227 Hom.: 76

Bravo AF: 0.0242

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital stromal corneal dystrophy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.5
DANN	Benign	0.88
PhyloP100		0.27
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1803343; hg19: chr12-91539784;