Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000133114 | SCV001712035 | likely pathogenic | Rett syndrome | 2023-10-13 | reviewed by expert panel | curation | The p.Asp151Gly variant in MECP2 (NM_004992.3) has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID 15173251) (PP4). The p.Asp151Gly variant has been observed in at least 3 other individuals with atypical Rett syndrome or clinical features of Rett syndrome (PMID 15173251, 32472557, internal database - University of Chicago, internal database - Invitae) (PS4_Moderate). The p.Asp151Gly variant occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of MECP2 (PM1). The p.Asp151Gly variant in MECP2 is absent from gnomAD (PM2_Supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Asp151Gly variant in MECP2 is classified as Likely Pathogenic based on the ACMG/AMP criteria (PS4_moderate, PM1, PM2_supporting, PP3, PP4). |
Genetic Services Laboratory, |
RCV000133114 | SCV000595748 | likely pathogenic | Rett syndrome | 2016-03-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000801156 | SCV000940922 | uncertain significance | Severe neonatal-onset encephalopathy with microcephaly | 2021-08-31 | criteria provided, single submitter | clinical testing | |
Centre for Population Genomics, |
RCV000133114 | SCV004098842 | likely pathogenic | Rett syndrome | 2023-08-14 | criteria provided, single submitter | curation | This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria.Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders to the ACMG/AMP Variant Interpretation Guidelines VCEP 2.0 , this variant is classified as Likely pathogenic. At least the following criteria are met: Occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of MECP2 (PM1). Has been observed in at least 3 individuals with phenotypes consistent with MECP2-related disease(PS4_Moderate). Computational prediction analysis tools suggests a deleterious impact (REVEL score ≥ 0.75) (PP3). This variant is absent from gnomAD (PM2_Supporting). |
Rett |
RCV000133114 | SCV000188105 | uncertain significance | Rett syndrome | 2008-01-21 | no assertion criteria provided | curation |