Submissions for variant NM_000038.6(APC):c.5864del (p.Ala1955fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002353427	SCV002654270	pathogenic	Hereditary cancer-predisposing syndrome	2025-02-20	criteria provided, single submitter	clinical testing	The c.5864delC pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of one nucleotide at nucleotide position 5864, causing a translational frameshift with a predicted alternate stop codon (p.A1955Vfs*15). This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 31% of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This variant was reported in individual(s) with features consistent with familial adenomatous polyposis (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this variant is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV004565308	SCV004045215	pathogenic	Familial adenomatous polyposis 1	2023-05-15	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
All of Us Research Program, National Institutes of Health	RCV004005708	SCV004831347	pathogenic	Classic or attenuated familial adenomatous polyposis	2023-06-26	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 16 of the APC gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.