Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV000258826 | SCV001430748 | likely pathogenic | Intellectual disability, autosomal recessive 57 | 2020-05-27 | criteria provided, single submitter | research | The homozygous p.Leu43HisfsTer69 variant in MBOAT7 was identified by our study in 2 siblings with autosomal recessive intellectual disability (PMID: 27616480), and segregated with disease in 3 affected relatives from a consanguineous family (PMID: 27616480). This variant was absent from large population studies and has also been reported pathogenic by OMIM in ClinVar (Variation ID: 268111). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 43 and leads to a premature termination codon 69 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. While there is some evidence to suggest that loss of function of the MBOAT7 gene is a disease mechanism in autosomal recessive intellectual disability, this association is not yet strongly established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1_Strong, PM2, PM3_Supporting, PP1 (Richards 2015). |
| OMIM | RCV000258826 | SCV000328566 | pathogenic | Intellectual disability, autosomal recessive 57 | 2022-01-26 | no assertion criteria provided | literature only |