ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2795C>A (p.Ser932Ter)

gnomAD frequency: 0.00001  dbSNP: rs878853432
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004564054 SCV000552484 pathogenic Familial adenomatous polyposis 1 2023-04-26 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. 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. ClinVar contains an entry for this variant (Variation ID: 411362). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1316610, 1338764, 10083733, 20685668). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser932*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1912 amino acid(s) of the APC protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506242 SCV000600065 pathogenic not provided 2017-06-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002436457 SCV002748321 pathogenic Hereditary cancer-predisposing syndrome 2023-03-09 criteria provided, single submitter clinical testing The p.S932* pathogenic mutation (also known as c.2795C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 2795. This changes the amino acid from a serine to a stop codon within coding exon 15. This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 1911 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This mutation has been previously identified in a patient with a clinical diagnosis of Familial Adenomatous Polyposis (FAP) (Miyoshi Y et al. Proc. Natl. Acad. Sci. U.S.A. 1992 May;89:4452-6; Lagarde A et al. J. Med. Genet. 2010 Oct;47:721-2). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV004564054 SCV004045642 pathogenic Familial adenomatous polyposis 1 2023-05-05 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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