Submissions for variant NM_006231.4(POLE):c.3582+17A>G

gnomAD frequency: 0.97472  dbSNP: rs5744889

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000442172	SCV000517994	benign	not specified	2015-10-30	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	RCV000586592	SCV000698672	benign	not provided	2016-05-19	criteria provided, single submitter	clinical testing	Variant summary: The POLE c.3582+17A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 117844/121342 control chromosomes (57239 homozygotes) at a frequency of 0.9711724, which is approximately 68370 times the estimated maximal expected allele frequency of a pathogenic POLE variant (0.0000142), indicating this variant is the common allele and a benign polymorphism. Taken together, this variant is classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000442172	SCV000806762	benign	not specified	2016-10-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586592	SCV001470786	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000586592	SCV001716892	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789328	SCV002031648	benign	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789329	SCV002031649	benign	Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency	2021-10-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002450973	SCV002613606	benign	Hereditary cancer-predisposing syndrome	2015-06-03	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001509971	SCV004016679	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000586592	SCV005237239	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000442172	SCV001921210	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000442172	SCV001958088	benign	not specified		no assertion criteria provided	clinical testing