rs1557339887
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM4_SupportingPP5_Very_Strong
The NM_000202.8(IDS):c.476_478del(p.His159del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. H159H) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 23)
Consequence
IDS
NM_000202.8 inframe_deletion
NM_000202.8 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.97
Genes affected
IDS (HGNC:5389): (iduronate 2-sulfatase) This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PM1
?
In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 6 uncertain in NM_000202.8
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000202.8. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant X-149500977-GGAT-G is Pathogenic according to our data. Variant chrX-149500977-GGAT-G is described in ClinVar as [Pathogenic]. Clinvar id is 437443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDS | NM_000202.8 | c.476_478del | p.His159del | inframe_deletion | 4/9 | ENST00000340855.11 | |
IDS | NM_001166550.4 | c.206_208del | p.His69del | inframe_deletion | 4/9 | ||
IDS | NM_006123.5 | c.476_478del | p.His159del | inframe_deletion | 4/8 | ||
IDS | NR_104128.2 | n.645_647del | non_coding_transcript_exon_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDS | ENST00000340855.11 | c.476_478del | p.His159del | inframe_deletion | 4/9 | 1 | NM_000202.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Mucopolysaccharidosis, MPS-II Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences | - | - - |
Pathogenic, criteria provided, single submitter | literature only | Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova | Jun 07, 2024 | Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Supporting), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Protein length changes in a nonrepeat region or stop–loss variants (PM4_Strong), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate) - |
Pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Jun 07, 2017 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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