Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000008159 | SCV000220648 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2014-08-27 | criteria provided, single submitter | literature only | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000008159 | SCV000920011 | pathogenic | PMM2-congenital disorder of glycosylation | 2018-04-23 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.26G>A (p.Cys9Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was observed with an allele frequency of 4.2e-06 in 236634 control chromosomes (gnomAD and publications). The variant, c.26G>A, has been reported in the literature in multiple individuals affected with Congenital Disorder of Glycosylation Type 1a (Bjursell_2000, Vuillaumier-Barrot_2000). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 30%-50% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000008159 | SCV004205315 | pathogenic | PMM2-congenital disorder of glycosylation | 2022-08-12 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000008159 | SCV004296387 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-07-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PMM2 function (PMID: 10922383, 11715002). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMM2 protein function. ClinVar contains an entry for this variant (Variation ID: 7720). This missense change has been observed in individual(s) with congenital disorder of glycosylation type 1a (PMID: 10922383, 11715002). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs104894532, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 9 of the PMM2 protein (p.Cys9Tyr). |
| OMIM | RCV000008159 | SCV000028364 | pathogenic | PMM2-congenital disorder of glycosylation | 2000-08-01 | no assertion criteria provided | literature only |