12-91145681-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001920.5(DCN):c.*377T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 355,554 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (10 hom.)
• Consequence: DCN NM_001920.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-91145681-A-G is Benign according to our data. Variant chr12-91145681-A-G is described in ClinVar as [Benign]. Clinvar id is 310644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 783 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCN	NM_001920.5	c.*377T>C		3_prime_UTR_variant	8/8	ENST00000052754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCN	ENST00000052754.10	c.*377T>C		3_prime_UTR_variant	8/8	1	NM_001920.5	P1
DCN	ENST00000425043.5	c.*377T>C		3_prime_UTR_variant	4/4	1
DCN	ENST00000393155.6	c.*1110T>C		3_prime_UTR_variant, NMD_transcript_variant	7/7	1
DCN	ENST00000548218.1	c.*44T>C		3_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 783 AN: 152198 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00872

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00592 AC: 382 AN: 64504 Hom.: 3 AF XY: 0.00565 AC XY: 193 AN XY: 34144

Gnomad AFR exome AF: 0.00119

Gnomad AMR exome AF: 0.00346

Gnomad ASJ exome AF: 0.00111

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00318

Gnomad FIN exome AF: 0.00293

Gnomad NFE exome AF: 0.00990

Gnomad OTH exome AF: 0.00846

GnomAD4 exome AF: 0.00633 AC: 1286 AN: 203238 Hom.: 10 Cov.: 0 AF XY: 0.00608 AC XY: 708 AN XY: 116410

Gnomad4 AFR exome AF: 0.00193

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00445

Gnomad4 FIN exome AF: 0.00216

Gnomad4 NFE exome AF: 0.00828

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.00513 AC: 782 AN: 152316 Hom.: 2 Cov.: 32 AF XY: 0.00482 AC XY: 359 AN XY: 74490

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00870

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00366 Hom.: 4

Bravo AF: 0.00516

Asia WGS AF: 0.00116 AC: 4 AN: 3462

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 12, 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	-0.81
Cadd	Benign	9.2
Dann	Benign	0.79

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: rs35379812; hg19: chr12-91539458;