Submissions for variant NM_006231.4(POLE):c.6657+16C>T

gnomAD frequency: 0.34836  dbSNP: rs5745075

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000410858	SCV000488517	benign	Colorectal cancer, susceptibility to, 12	2016-04-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000420114	SCV000518003	benign	not specified	2015-11-03	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000420114	SCV000540079	benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587840	SCV000698687	benign	not provided	2016-05-19	criteria provided, single submitter	clinical testing	Variant summary: The POLE c.6657+16C>T variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant, and 5/5 Alamut algorithms predict no significant change to splicing. This variant was found in 44723/120770 control chromosomes (9098 homozygotes) at a frequency of 0.3703155, which is approximately 26070 times the estimated maximal expected allele frequency of a pathogenic POLE variant (0.0000142), highly suggesting this variant is a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV000420114	SCV000806844	benign	not specified	2016-10-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587840	SCV001470790	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Invitae	RCV000587840	SCV001730160	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789321	SCV002031629	benign	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789322	SCV002031632	benign	Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency	2021-10-25	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000410858	SCV004016682	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000420114	SCV001921471	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000420114	SCV001953843	benign	not specified		no assertion criteria provided	clinical testing