ClinVar

Description

The p.Glu18Profs*44 variant in the BPTF 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/). However, the ability to detect this type of variation may be limited. The p.Glu18Profs*44 variant results in a 10 bp deletion, which causes a shift in the protein reading frame, leading to a premature termination codon 44 amino acids downstream. The premature termination codon is in exon 1 of 28 coding exons, and is therefore predicted to undergo nonsense-mediated decay resulting in a truncated or absent protein. Heterozygous loss of function is an established mechanism of disease for the BPTF gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Glu18Profs*44 variant as pathogenic for autosomal dominant BPTFassociated neurodevelopmental disorder based on the information above. [ACMG evidence codes used: PVS1; PM2; PS2_Supporting]