rs111252008
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2
The NM_013352.4(DSE):βc.2619_2621delβ(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 (β β ). Synonymous variant affecting the same amino acid position (i.e. G873G) has been classified as Likely benign.
Frequency
Genomes: π 0.015 ( 46 hom., cov: 32)
Exomes π: 0.0017 ( 45 hom. )
Consequence
DSE
NM_013352.4 inframe_deletion
NM_013352.4 inframe_deletion
Scores
Not classified
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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: 2268AN: 152074Hom.: 43 Cov.: 32
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GnomAD3 exomes AF: 0.00415 AC: 1043AN: 251340Hom.: 21 AF XY: 0.00310 AC XY: 421AN XY: 135852
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GnomAD4 exome AF: 0.00170 AC: 2478AN: 1461858Hom.: 45 AF XY: 0.00152 AC XY: 1109AN XY: 727226
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GnomAD4 genome ? AF: 0.0151 AC: 2291AN: 152192Hom.: 46 Cov.: 32 AF XY: 0.0150 AC XY: 1113AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2018 | - - |
Benign, flagged submission | clinical testing | GeneDx | May 31, 2017 | - - |
DSE-related disorder Benign:1
Benign, criteria provided, single submitter | 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 | Invitae | Jan 31, 2024 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at