Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780609 | SCV000918025 | pathogenic | PMM2-congenital disorder of glycosylation | 2021-10-18 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.640-9T>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant weakens a 3 acceptor site. Experimental evidence supports these predictions demonstrating that the variant affects mRNA splicing (Vega_2009). The variant allele was found at a frequency of 4e-06 in 251000 control chromosomes (gnomAD). c.640-9T>G has been reported in the literature in individuals affected with Congenital Disorder Of Glycosylation Type 1a (e.g. Richard_2009, Perez_2011, Perez-Cerda_2017). These data indicate that the variant is likely to be associated with disease. A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000780609 | SCV001163406 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-11-09 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000780609 | SCV001387044 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-09-29 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 7 of the PMM2 gene. It does not directly change the encoded amino acid sequence of the PMM2 protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs370160676, gnomAD 0.003%). This variant has been observed in individual(s) with congenital disorder of glycosylation type 1a (PMID: 19235233). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 632945). Studies have shown that this variant results in skipping of exon 8 and introduces a new termination codon (PMID: 19235233). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV000780609 | SCV002060136 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2021-11-08 | criteria provided, single submitter | clinical testing | NM_000303.2(PMM2):c.640-9T>G is an intronic variant classified as likely pathogenic in the context of congenital disorder of glycosylation type Ia. c.640-9T>G has been observed in cases with relevant disease (PMID: 29701302, 19235233). Functional assessments of this variant are available in the literature (PMID: 19235233, 21541725). c.640-9T>G has been observed in population frequency databases (gnomAD: NFE 0.001%). In summary, NM_000303.2(PMM2):c.640-9T>G is an intronic variant that has functional support for pathogenicity and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
| Fulgent Genetics, |
RCV000780609 | SCV002787067 | pathogenic | PMM2-congenital disorder of glycosylation | 2022-05-10 | criteria provided, single submitter | clinical testing |