ClinVar

Description

This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. Similar deletions of exon 16 have been observed in individuals affected with clinical features of familial adenomatous polyposis (PMID: 15689459, 17568392). Exon 16 has also been reported as exon 15 in the literature. This variant is a gross deletion of the genomic region encompassing part of exon 16 of the APC gene. The 5' end of this event occurs in exon 16 (c.2639) of the APC gene. The 3' end of this event extends through the termination codon beyond the assayed region for this gene. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation.