Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589576 | SCV000696498 | uncertain significance | not provided | 2016-03-25 | criteria provided, single submitter | clinical testing | Variant Summary: This PMM2 variant affects a non-conserved nucleotide, resulting in an amino acid change from Ile to Met. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). Functional studies on this variant have not been carried out. This variant was found in 2/31948 control chromosomes at a frequency of 0.0000626, which does not exceed the maximal allele frequency of a pathogenic PMM2 variant (0.0055902). This variant has been reported in one patient with intellectual disability without a second pathogenic allele (Redin_2014) and authors predict the variant to be possibly benign. Because of limited clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available. |
Invitae | RCV001271491 | SCV001557679 | uncertain significance | PMM2-congenital disorder of glycosylation | 2022-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 142 of the PMM2 protein (p.Ile142Met). This variant is present in population databases (rs781610241, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PMM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 495798). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Natera, |
RCV001271491 | SCV001452680 | uncertain significance | PMM2-congenital disorder of glycosylation | 2019-12-30 | no assertion criteria provided | clinical testing |