Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670499 | SCV000795356 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2017-11-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000670499 | SCV001203909 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr64Thrfs*11) 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 0.003%). This premature translational stop signal has been observed in individual(s) with congenital disorders of glycosylation (PMID: 28139241). ClinVar contains an entry for this variant (Variation ID: 554804). 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. |
| Fulgent Genetics, |
RCV000670499 | SCV001752707 | pathogenic | PMM2-congenital disorder of glycosylation | 2021-06-30 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003411579 | SCV004114357 | likely pathogenic | PMM2-related disorder | 2022-09-20 | criteria provided, single submitter | clinical testing | The PMM2 c.190delT variant is predicted to result in a frameshift and premature protein termination (p.Tyr64Thrfs*11). This variant was reported in an individual with congenital disorder of glycosylation 1a (Pérez-Cerdá et al. 2017. PubMed ID: 28139241). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-8898634-AT-A). Frameshift variants in PMM2 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |
| Baylor Genetics | RCV000670499 | SCV004205310 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2024-01-24 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000670499 | SCV004847442 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2024-02-10 | criteria provided, single submitter | clinical testing | The p.Tyr64ThrfsX11 variant in PMM2 has been reported in 1 individual with congenital disorder of glycosylation, with no additional information about whether any other variants were identified (Perez-Cerda 2017 PMID: 28139241). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 554804) and was absent from large population studies (gnomAD v.3.1.2). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 64 and leads to a premature termination codon 11 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function of the PMM2 gene is an established disease mechanism in autosomal recessive PMM2-congential disorder of glycosylation. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive PMM2-congential disorder of glycosylation. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |