Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002826796 | SCV003600889 | likely pathogenic | Inborn genetic diseases | 2022-03-04 | criteria provided, single submitter | clinical testing | The c.1412G>A (p.W471*) alteration, located in exon 1 (coding exon 1) of the IRF2BPL gene, consists of a G to A substitution at nucleotide position 1412. This changes the amino acid from a tryptophan (W) to a stop codon at amino acid position 471. Premature stop codons are typically deleterious in nature; however, because IRF2BPL is a single-exon gene this alteration is not expected to trigger nonsense-mediated mRNA decay and a truncated protein could still be expressed (Maquat, 2004). This alteration removes the last 325 amino acids of the protein and the exact functional impact of these amino acids is unknown at this time; however, structural analysis suggests this variant disrupts a functional motif. 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 likely pathogenic. |