6-116426078-A-G

Variant names:

• chr6-116426078-A-G
• rs508521
• NM_013352.4:c.417-496A>G

Variant summary

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

The NM_013352.4(DSE):​c.417-496A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,084 control chromosomes in the GnomAD database, including 39,346 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 0.71 (39346 hom., cov: 32)
• Consequence: DSE NM_013352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 9 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: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285446 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013352.4. 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_013352.4	MANE Select	c.417-496A>G		intron	N/A	NP_037484.1
	DSE	NM_001322939.2		c.474-496A>G		intron	N/A	NP_001309868.1
	DSE	NM_001080976.3		c.417-496A>G		intron	N/A	NP_001074445.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSE	ENST00000644252.3	MANE Select	c.417-496A>G		intron	N/A	ENSP00000494147.2
	DSE	ENST00000452085.7	TSL:1	c.417-496A>G		intron	N/A	ENSP00000404049.2
	DSE	ENST00000359564.3	TSL:1	c.417-496A>G		intron	N/A	ENSP00000352567.3

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108501 AN: 151966 Hom.: 39306 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.714 AC: 108593 AN: 152084 Hom.: 39346 Cov.: 32 AF XY: 0.711 AC XY: 52842 AN XY: 74322

African (AFR) AF: 0.784 AC: 32537 AN: 41482

American (AMR) AF: 0.748 AC: 11422 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2560 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2236 AN: 5168

South Asian (SAS) AF: 0.502 AC: 2422 AN: 4822

European-Finnish (FIN) AF: 0.722 AC: 7633 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47622 AN: 67982

Other (OTH) AF: 0.690 AC: 1459 AN: 2116

Alfa AF: 0.703 Hom.: 64275

Bravo AF: 0.720

Asia WGS AF: 0.515 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.43
PhyloP100		-0.15
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: rs508521; hg19: chr6-116747241;