6-116293138-A-G

Variant names:

• chr6-116293138-A-G
• rs4326261
• ENST00000452085.7:c.-54+12878A>G

Variant summary

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

The NM_001080976.3(DSE):​c.-54+12878A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 152,306 control chromosomes in the GnomAD database, including 72,917 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 0.98 (72917 hom., cov: 33)
• Consequence: DSE NM_001080976.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 0 publications found

Genes affected

DSE (HGNC:21144): (dermatan sulfate epimerase) The protein encoded by this gene is a tumor-rejection antigen. It is localized to the endoplasmic reticulum and functions to convert D-glucuronic acid to L-iduronic acid during the biosynthesis of dermatan sulfate. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. Mutations in this gene cause inmusculocontractural Ehlers-Danlos syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 9, and a paralogous gene exists on chromosome 18. [provided by RefSeq, Apr 2016]

DSE Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, musculocontractural type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080976.3. 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
	DSE	NM_001080976.3		c.-54+12878A>G		intron	N/A	NP_001074445.1	Q9UL01
	DSE	NM_001322937.2		c.-54+34171A>G		intron	N/A	NP_001309866.1	Q9UL01
	DSE	NM_001322938.2		c.-54+34171A>G		intron	N/A	NP_001309867.1	Q9UL01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSE	ENST00000452085.7	TSL:1	c.-54+12878A>G		intron	N/A	ENSP00000404049.2	Q9UL01
	DSE	ENST00000449314.5	TSL:1	n.62+12878A>G		intron	N/A
	DSE	ENST00000891542.1		c.-54+34171A>G		intron	N/A	ENSP00000561601.1

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148824 AN: 152188 Hom.: 72867 Cov.: 33

Gnomad AFR AF: 0.922

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.978 AC: 148933 AN: 152306 Hom.: 72917 Cov.: 33 AF XY: 0.979 AC XY: 72924 AN XY: 74482

African (AFR) AF: 0.922 AC: 38319 AN: 41540

American (AMR) AF: 0.993 AC: 15187 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10622 AN: 10622

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68027 AN: 68034

Other (OTH) AF: 0.985 AC: 2085 AN: 2116

Alfa AF: 0.986 Hom.: 4388

Bravo AF: 0.975

Asia WGS AF: 0.996 AC: 3460 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.54
PhyloP100		-0.36
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: rs4326261; hg19: chr6-116614301;