Submissions for variant NM_000038.6(APC):c.3165A>T (p.Ile1055=)

gnomAD frequency: 0.00286  dbSNP: rs61734287

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003315712	SCV000153970	benign	Familial adenomatous polyposis 1	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000211906	SCV000167004	benign	not specified	2014-02-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000129160	SCV000183890	benign	Hereditary cancer-predisposing syndrome	2014-11-24	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202973	SCV000257784	benign	Familial multiple polyposis syndrome	2015-03-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307559	SCV000452000	benign	APC-Associated Polyposis Disorders	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000211906	SCV000602504	benign	not specified	2019-02-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129160	SCV000681582	benign	Hereditary cancer-predisposing syndrome	2016-03-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000211906	SCV000805388	benign	not specified	2016-11-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001529443	SCV001746824	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	APC: BP4, BP7, BS1
Genetic Services Laboratory, University of Chicago	RCV000211906	SCV002069698	benign	not specified	2020-04-22	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000129160	SCV002532488	benign	Hereditary cancer-predisposing syndrome	2020-08-26	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000211906	SCV002550611	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315712	SCV004015691	benign	Familial adenomatous polyposis 1	2023-07-07	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000129160	SCV004228055	benign	Hereditary cancer-predisposing syndrome	2023-12-12	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353666	SCV000591131	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC, p.Ile1055Ile variant was not identified in the literature nor was it identified in the GeneInsight COGR through the Canadian Open Genetics Repository, CLINVITAE, COSMIC or MutDB databases. The variant was identified in dbSNP (ID: rs61734287 “With Benign allele”, with a minor allele frequency of 0.001(5 of 5000 in 1000 Genomes Project). In NHLBI Exome Sequencing Project (Exome Variant Server) the variant was identified in 34 of 8600 European Americans and 4 of 4405 African Americans. In the Exome Aggregation Consortium (ExAC) database (released Oct 20th, 2014), the variant was identified in 428 of 120724 chromosomes (frequency: 0.003545) (or 394 of 66424 alleles in the European (Non-Finnish) - 2 of them homozygous, 17 of 6610 alleles in the European (Finnish), 7 of 10258 of Africans, 6 of 11508 Latinos, 4 of 16456 South Asians), increasing the likelihood this could be a low frequency benign variant. The variant was also identified in the Clinvar database and classified as benign by Invitae, by Gene DX and by Ambry genetics; classified as neutral in UMD database and co-occurred with a pathogenic variant - APC: c.1248C>G, p.Tyr416X. It was identified 2X in InSiGHT Colon Cancer Database and 1X in Zhejiang Colon Cancer Database.The p.Ile1055Ile variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000211906	SCV000691730	likely benign	not specified		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000129160	SCV000693475	likely benign	Hereditary cancer-predisposing syndrome	2017-09-11	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529443	SCV001742912	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001529443	SCV001800609	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000211906	SCV001807284	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001529443	SCV001922002	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529443	SCV001958003	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000211906	SCV001972576	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000211906	SCV002033980	benign	not specified		no assertion criteria provided	clinical testing