Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000675031 | SCV000800460 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2018-06-07 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000675031 | SCV001426863 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2021-10-17 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.451_454delGAAA (p.Glu151IlefsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251184 control chromosomes. c.451_454delGAAA has been reported in the literature as a compound heterozygous genotype in at-least one in individual affected with Congenital Disorder Of Glycosylation Type 1a and has been subsequently cited by others (example, Callewaert_2003, Schollen_2002). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV000675031 | SCV002110727 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu151Ilefs*2) in the PMM2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMM2 are known to be pathogenic (PMID: 19862844). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with PMM2-related conditions (PMID: 12626389). ClinVar contains an entry for this variant (Variation ID: 558721). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000675031 | SCV004205267 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-11-13 | criteria provided, single submitter | clinical testing |