Submissions for variant NM_000038.6(APC):c.2684C>G (p.Ser895Ter)

dbSNP: rs2149875189

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratorio de Genética Hospitales Universitarios Virgen de las Nieves y Clínico San Cecilio (Granada, Spain), Hospitales Universitarios Virgen de las Nieves y Clínico San Cecilio (Granada, Spain)	RCV001580136	SCV001797287	likely pathogenic	Familial adenomatous polyposis 1	2021-05-31	criteria provided, single submitter	clinical testing	APC(NM_000038.5):c.2684C>G (p.Ser895Ter) is a null variant (nonsense), in gene APC for which loss-of-function is a known mechanism of disease. This variant is not found in gnomAD exomes and gnomAD genomes. We have found pathogenic computational verdict based on 5 pathogenic predictions from BayesDel_addAF, CADD, EIGEN, FATHMM-MKL and MutationTaster vs no benign predictions. Individual with multiple colorectal adenomatous polyps identified by colonoscopy mostly tubular histological type. With family history of colorectal polyps and colorectal cancer.
Myriad Genetics, Inc.	RCV001580136	SCV004045536	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001580136	SCV005839569	pathogenic	Familial adenomatous polyposis 1	2025-01-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser895*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1949 amino acid(s) of the APC protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1210113). This variant disrupts a region of the APC protein in which other variant(s) (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 1316610, 8381579, 9824584, 22135120, 27081525). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.