chr12-91179286-C-G

Position:

• chr12-91179286-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCN	NM_001920.5	c.-33-701G>C		intron_variant		ENST00000052754.10	NP_001911.1
DCN	NM_133503.4	c.-34+76G>C		intron_variant			NP_598010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCN	ENST00000052754.10	c.-33-701G>C		intron_variant		1	NM_001920.5	ENSP00000052754	P1

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0519

Gnomad4 OTH exome AF: 0.0833

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

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0658

Gnomad4 FIN AF: 0.0441

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.120

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.50

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: rs2070985; hg19: chr12-91573063;