Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genomics Laboratory, |
RCV003492903 | SCV004232358 | pathogenic | Cardiac anomalies - developmental delay - facial dysmorphism syndrome | 2021-04-12 | criteria provided, single submitter | clinical testing | The p.Asn1154Metfs*15 variant in the MED13L 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/). The p.Asn1154Metfs*15 variant results in a 1bp deletion, which causes a shift in the protein reading frame, leading to a premature termination codon 15 amino acids downstream. Heterozygous loss of function is an established mechanism of disease for the MED13L gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Asn1154Metfs*15 variant as pathogenic for autosomal dominant MED13L-related intellectual disability based on the information above. [ACMG evidence codes used: PVS1; PS2_moderate; PM2] |