Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV004018267 | SCV007539173 | pathogenic | Mucopolysaccharidosis, MPS-II | 2026-03-02 | criteria provided, single submitter | research | The hemizygous c.418+1_418+4del variant in IDS was identified in 1 individual with mucopolysaccharidosis type II via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the NeuroDev Study (https://www.neurodevproject.org/). The phenotype of this individual is highly specific for mucopolysaccharidosis type II based on abnormal urine glycosaminoglycan (GAG) analysis. The c.418+1_418+4del variant in IDS has not been previously reported in the literature in individuals with mucopolysaccharidosis type 2 and was absent from large population studies. This variant is located in the 3' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine/rule out pathogenicity. Loss of function of the IDS gene is an established disease mechanism in X-linked recessive mucopolysaccharidosis type 2. In summary, this variant meets criteria to be classified as pathogenic for X-linked recessive mucopolysaccharidosis type 2. ACMG/AMP Criteria applied: PVS1, PP4, PM2_supporting, PS4_supporting (Richards 2015). |
| Laboratory for Molecular Medicine, |
RCV004018267 | SCV004847310 | pathogenic | Mucopolysaccharidosis, MPS-II | 2023-08-28 | criteria provided, single submitter | clinical testing | The c.418+1_418+4delGTAC variant in IDS has been observed in one individual with a clinical and biochemical diagnosis of Mucopolysaccharidosis Type II (LMM data) and was absent from large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the IDS gene is an established disease mechanism in X-linked Mucopolysaccharidosis Type II. Although this particular variant is absent from ClinVar, variants c.418+1G>C (Variation ID 664872) and c.418+2T>C (Variant ID 997091) which disrupt invariant donor splice sites of exon 3 have been reported as pathogenic by other labs. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as pathogenic for X-linked Mucopolysaccharidosis Type II. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PS4_Supporting, PP4. |