chr12-91179286-C-G

Variant names:

• chr12-91179286-C-G
• rs2070985
• NM_001920.5:c.-33-701G>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.-33-701G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,514 control chromosomes in the GnomAD database, including 1,407 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 0.12 (1407 hom., cov: 32)
  • Exomes 𝑓: 0.061 (0 hom.)
• Consequence: DCN NM_001920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 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.-33-701G>C		intron	N/A	NP_001911.1
	DCN	NM_133503.4		c.-34+76G>C		intron	N/A	NP_598010.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCN	ENST00000052754.10	TSL:1 MANE Select	c.-33-701G>C		intron	N/A	ENSP00000052754.5
	DCN	ENST00000393155.6	TSL:1	n.-33-701G>C		intron	N/A	ENSP00000376862.2
	DCN	ENST00000970672.1		c.-34+76G>C		intron	N/A	ENSP00000640731.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17696 AN: 152088 Hom.: 1398 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.0613 AC: 19 AN: 310 Hom.: 0 Cov.: 0 AF XY: 0.0613 AC XY: 13 AN XY: 212

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.143 AC: 2 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0519 AC: 14 AN: 270

Other (OTH) AF: 0.0833 AC: 1 AN: 12

GnomAD4 genome AF: 0.117 AC: 17736 AN: 152204 Hom.: 1407 Cov.: 32 AF XY: 0.114 AC XY: 8447 AN XY: 74408

African (AFR) AF: 0.219 AC: 9082 AN: 41504

American (AMR) AF: 0.105 AC: 1606 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.139 AC: 718 AN: 5174

South Asian (SAS) AF: 0.0658 AC: 317 AN: 4820

European-Finnish (FIN) AF: 0.0441 AC: 468 AN: 10614

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4677 AN: 68014

Other (OTH) AF: 0.120 AC: 253 AN: 2112

Alfa AF: 0.0915 Hom.: 143

Bravo AF: 0.128

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.50
PhyloP100		0.38
PromoterAI		0.019	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: rs2070985; hg19: chr12-91573063;