Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004987964 | SCV005605058 | pathogenic | Inborn genetic diseases | 2024-11-12 | criteria provided, single submitter | clinical testing | The c.2052delGinsAA (p.P685Tfs*5) alteration, located in exon 1 (coding exon 1) of the IRF2BPL gene, consists of an deletion of 1 and insertion of 2 nucleotides causing a translational frameshift at position 2052 with a predicted alternate stop codon after 5 amino acids. Because IRF2BPL is a single-exon gene, this alteration is not expected to trigger nonsense-mediated mRNA decay and an altered protein could still be expressed (Maquat, 2004). However, frameshifts are typically deleterious in nature, the impacted region is critical for protein function, and a significant portion of the protein (14.1%) is affected (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. |