rs483352904
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000202.8(IDS):c.509_510del(p.Thr170MetfsTer28) variant causes a frameshift, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
IDS
NM_000202.8 frameshift, splice_region
NM_000202.8 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.24
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-149498304-ATG-A is Pathogenic according to our data. Variant chrX-149498304-ATG-A is described in ClinVar as [Pathogenic]. Clinvar id is 10496.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-149498304-ATG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDS | NM_000202.8 | c.509_510del | p.Thr170MetfsTer28 | frameshift_variant, splice_region_variant | 5/9 | ENST00000340855.11 | |
IDS | NM_001166550.4 | c.239_240del | p.Thr80MetfsTer28 | frameshift_variant, splice_region_variant | 5/9 | ||
IDS | NM_006123.5 | c.509_510del | p.Thr170MetfsTer28 | frameshift_variant, splice_region_variant | 5/8 | ||
IDS | NR_104128.2 | n.678_679del | splice_region_variant, non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDS | ENST00000340855.11 | c.509_510del | p.Thr170MetfsTer28 | frameshift_variant, splice_region_variant | 5/9 | 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:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mucopolysaccharidosis, MPS-II Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 1992 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at