Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665521 | SCV000789659 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2017-02-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000665521 | SCV001574941 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2024-01-22 | 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 results in the gain of 41 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with congenital disorder of glycosylation type 1a (PMID: 17307006, 33643843). 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: 550704). Studies have shown that this variant results in the activation of a cryptic splice site in intron 7 (PMID: 19235233). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000665521 | SCV002103446 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2022-02-08 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.640-15479C>T is located at a position not widely known to affect splicing. However, several computational tools predict a significant impact on normal splicing: Three predict the variant creates a 5' donor site and one predict the variant strengthens a 5' donor site. Functional studies have shown the variant to result in the creation of a pseudoexon, an additional 123 bp between exon 7 and 8 (Schollen_2007, Vega_2008). The variant was absent in 31398 control chromosomes. c.640-15479C>T has been reported in the literature in individuals affected with Congenital Disorder Of Glycosylation Type 1a (Schollen_2007, Lipinski_2021). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV000665521 | SCV002809258 | pathogenic | PMM2-congenital disorder of glycosylation | 2021-11-03 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000665521 | SCV004204829 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2023-10-29 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000665521 | SCV000028368 | pathogenic | PMM2-congenital disorder of glycosylation | 2009-05-01 | no assertion criteria provided | literature only | |
| Natera, |
RCV000665521 | SCV002092442 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2020-02-11 | no assertion criteria provided | clinical testing |