Submissions for variant NM_006231.4(POLE):c.1359+9G>A

gnomAD frequency: 0.00498  dbSNP: rs75135381

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000587865	SCV000262354	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Counsyl	RCV000204657	SCV000489226	benign	Colorectal cancer, susceptibility to, 12	2016-09-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000430978	SCV000518047	likely benign	not specified	2017-12-11	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587865	SCV000698661	benign	not provided	2017-05-23	criteria provided, single submitter	clinical testing	Variant summary: The POLE c.1359+9G>A variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 174/120428 control chromosomes (2 homozygotes) from ExAC at a frequency of 0.0014448, which is approximately 102 times the estimated maximal expected allele frequency of a pathogenic POLE variant (0.0000142), strongly suggesting this variant is likely a benign polymorphism. It is primarily found in African subpopulation with an allele frequency of 0.015 (161/10296 chromosomes). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000430978	SCV000806718	benign	not specified	2017-07-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000430978	SCV000888496	benign	not specified	2022-03-16	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002503819	SCV002811762	likely benign	Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency	2022-05-17	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000204657	SCV004017088	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000204657	SCV004018508	likely benign	Colorectal cancer, susceptibility to, 12	2023-04-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000430978	SCV004027366	benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005361212	SCV005915727	likely benign	POLE-related polyposis and colorectal cancer syndrome	2019-11-15	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000587865	SCV001919207	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000430978	SCV001968621	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000430978	SCV001977736	benign	not specified		no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000430978	SCV003839898	benign	not specified	2022-06-20	no assertion criteria provided	clinical testing