rs741212

Variant names:

• chr12-91180965-A-G
• rs741212
• NM_001920.5:c.-34+1690T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463
• Publications: 6 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000293802 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001920.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	NM_001920.5	MANE Select	c.-34+1690T>C		intron	N/A	NP_001911.1	P07585-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	ENST00000052754.10	TSL:1 MANE Select	c.-34+1690T>C		intron	N/A	ENSP00000052754.5	P07585-1
	DCN	ENST00000393155.6	TSL:1	n.-34+1690T>C		intron	N/A	ENSP00000376862.2	A0A7I2PRI8
	DCN	ENST00000549513.5	TSL:4	c.-551T>C		5_prime_UTR	Exon 1 of 4	ENSP00000449438.1	F8VX58

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12621 AN: 152132 Hom.: 728 Cov.: 32

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0829 AC: 12614 AN: 152250 Hom.: 727 Cov.: 32 AF XY: 0.0803 AC XY: 5976 AN XY: 74440

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: 8 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: 30 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8580 AN: 67994

Other (OTH) AF: 0.108 AC: 228 AN: 2116

Alfa AF: 0.110 Hom.: 567

Bravo AF: 0.0852

Asia WGS AF: 0.0160 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.82
PhyloP100		0.46
PromoterAI		0.0048	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs741212;

hg19: chr12-91574742;