Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV003098851 | SCV005089660 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2024-06-07 | criteria provided, single submitter | literature only | 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), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate) |
| Labcorp Genetics |
RCV003098851 | SCV003445849 | pathogenic | Mucopolysaccharidosis, MPS-II | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 80 of the IDS protein (p.Gln80Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of mucopolysaccharidosis type II (PMID: 22976768, 24125893, 27883178). ClinVar contains an entry for this variant (Variation ID: 1790667). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Gln80 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 22286622), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002430660 | SCV002731487 | likely pathogenic | Inborn genetic diseases | 2016-05-18 | criteria provided, single submitter | clinical testing | The p.Q80R variant (also known as c.239A>G), located in coding exon 2 of the IDS gene, results from an A to G substitution at nucleotide position 239. The glutamine at codon 80 is replaced by arginine, an amino acid with highly similar properties. This variant was detected in two individuals, one with a clinical diagnosis of Hunter syndrome and absent IDS activity and the second with a clinical suspicion of a mucopolysaccharidosis due to elevated levels of heparan and dermatan sulfate in urine (Pollard LM, J. Inherit. Metab. Dis. 2013 Mar; 36(2):179-87). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |