Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001775246 | SCV002011958 | likely pathogenic | Ayme-Gripp syndrome | 2021-10-02 | criteria provided, single submitter | clinical testing | The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Thr62Arg) has been reported as pathogenic/likely pathogenic with supporting evidence (ClinVar ID: VCV000162517.1, PM5_P). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.87, 3Cnet: 0.892, PP3). Patient's phenotype is considered compatible with Ayme-Gripp syndrome (3billion dataset, PP4).Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV002541042 | SCV003317070 | likely pathogenic | Cataract 21 multiple types; Ayme-Gripp syndrome | 2022-04-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1320073). This missense change has been observed in individual(s) with clinical features of Ayme-Gripp syndrome (PMID: 34217267; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 62 of the MAF protein (p.Thr62Met). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Thr62 amino acid residue in MAF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25865493). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). |
| DECIPHERD- |
RCV001775246 | SCV004171009 | likely pathogenic | Ayme-Gripp syndrome | 2023-07-01 | criteria provided, single submitter | research |