Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000899427 | SCV001043693 | benign | Mucopolysaccharidosis, MPS-II | 2024-01-03 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271596 | SCV002556015 | likely benign | not specified | 2022-06-02 | criteria provided, single submitter | clinical testing | Variant summary: IDS c.851C>T (p.Pro284Leu) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.7e-05 in 183363 control chromosomes, predominantly at a frequency of 0.0012 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in IDS causing Mucopolysaccharidosis Type II (Hunter Syndrome) (8.7e-05 vs 0.0029), allowing no conclusion about variant significance. c.851C>T has been reported in the literature as a pseudo-deficiency allele that has been associated with an attenuated phenotype in at-least one individual reportedly affected with Mucopolysaccharidosis Type II (Hunter Syndrome) (example, Kosuga_2016) and as a VUS in settings of newborn screening (NBS) among infants not meeting the confirmatory criteria for a typical MPS II diagnosis (example, Yu Lin_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type II (Hunter Syndrome). At least one publication reports experimental evidence evaluating an impact on protein function (Yu Lin_2020). The most pronounced variant effect results in 62% of normal activity. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Ambry Genetics | RCV002444996 | SCV002679144 | likely benign | Inborn genetic diseases | 2018-02-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000899427 | SCV005089271 | 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_Moderate), 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_Strong), In vitro or in vivo functional studies showing no damaging effect (BS3_Supporting) |