Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genomics Laboratory, |
RCV003389030 | SCV004100856 | pathogenic | Intellectual disability, autosomal dominant 1 | 2020-11-19 | no assertion criteria provided | clinical testing | The p.Ser1416Thrfs*12 variant in the MBD5 gene was identified de novo in this individual, but has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). This variant leads to a premature stop codon in exon 12 of 15, and is therefore predicted to undergo nonsense-medicated decay resulting in a truncated or absent protein. Heterozygous loss of function is an established mechanism of disease for the MBD5 gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Ser1416Thrfs*12 variant as pathogenic for autosomal dominant MBD5-associated neurodevelopmental disorder based on the information above. [ACMG: PVS1, PS2_Supporting; PM2] |