rs111252008

Positions:

• chr6-116437084-TGGG-T
• chr6-116437084-TGGG-TGGGGGG

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The NM_013352.4(DSE):​c.2619_2621del​(p.Gly874del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00295 in 1,614,050 control chromosomes in the GnomAD database, including 91 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G873G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.015 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (45 hom.)
• Consequence: DSE NM_013352.4 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.35

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_013352.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 6-116437084-TGGG-T is Benign according to our data. Variant chr6-116437084-TGGG-T is described in ClinVar as [Benign]. Clinvar id is 474683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-116437084-TGGG-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0151 (2291/152192) while in subpopulation AFR AF= 0.0508 (2109/41516). AF 95% confidence interval is 0.049. There are 46 homozygotes in gnomad4. There are 1113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSE	NM_013352.4	c.2619_2621del	p.Gly874del	inframe_deletion	6/6	ENST00000644252.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSE	ENST00000644252.3	c.2619_2621del	p.Gly874del	inframe_deletion	6/6		NM_013352.4	P1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2268 AN: 152074 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.00982

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00415 AC: 1043 AN: 251340 Hom.: 21 AF XY: 0.00310 AC XY: 421 AN XY: 135852

Gnomad AFR exome AF: 0.0503

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00744

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00170 AC: 2478 AN: 1461858 Hom.: 45 AF XY: 0.00152 AC XY: 1109 AN XY: 727226

Gnomad4 AFR exome AF: 0.0498

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.00777

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000150

Gnomad4 OTH exome AF: 0.00435

GnomAD4 genome AF: 0.0151 AC: 2291 AN: 152192 Hom.: 46 Cov.: 32 AF XY: 0.0150 AC XY: 1113 AN XY: 74428

Gnomad4 AFR AF: 0.0508

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00982

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00232 Hom.: 1

Bravo AF: 0.0167

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, flagged submission	clinical testing	GeneDx	May 31, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 05, 2018	- -

DSE-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Ehlers-Danlos syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 17, 2022

- -

Ehlers-Danlos syndrome, musculocontractural type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs111252008; hg19: chr6-116758247;