Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001384753 | SCV001584397 | pathogenic | not provided | 2020-03-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect CCND2 protein function (PMID: 24705253). This variant has been observed in individual(s) with clinical features of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome (PMID: 24705253, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 143985). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 281 of the CCND2 protein (p.Pro281Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. |
| Prevention |
RCV003390829 | SCV004110535 | uncertain significance | CCND2-related disorder | 2023-01-15 | criteria provided, single submitter | clinical testing | The CCND2 c.842C>G variant is predicted to result in the amino acid substitution p.Pro281Arg. This variant, as well as additional variants at the same amino acid (p.Pro281Ser, p.Pro281Leu, and p.Pro281Ala) have been been documented in individuals with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) (Mirzaa et al. 2014. PubMed ID:24705253; Supplementary Table 3, Patient 21, Helbig et al. 2016. PubMed ID: 26795593; Sameshima et al. 2020. PubMed ID: 31957131). Of note, these variants were documented as de novo in some cases (Mirzaa et al. 2014. PubMed ID:24705253; Supplementary Table 3, Patient 21, Helbig et al. 2016. PubMed ID: 26795593) and in others inheritance was not noted or not determined. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. While this variant may be causative, given the mosaic nature, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| OMIM | RCV000133499 | SCV000188573 | pathogenic | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 | 2014-05-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000133499 | SCV000328929 | not provided | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 | no assertion provided | literature only |