Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001808280 | SCV002058942 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PMM2 related disorder (PMID:9497260, PS1_P). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 25681648, PM3_M). A different missense change at the same codon has been reported to be associated with PMM2 related disorder (PMID:11058895, PM5_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.723, PP3_P). A missense variant is a common mechanism associated with Congenital disorder of glycosylation (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000008, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV001808280 | SCV002238805 | pathogenic | PMM2-congenital disorder of glycosylation | 2022-03-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1333592). For these reasons, this variant has been classified as Pathogenic. 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. This missense change has been observed in individual(s) with congenital disorder of glycosylation Ia (PMID: 10066032, 25681648). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs151319324, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 238 of the PMM2 protein (p.Arg238Pro). |
| Baylor Genetics | RCV001808280 | SCV004205284 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-05-13 | criteria provided, single submitter | clinical testing |