Submissions for variant NM_006231.4(POLE):c.62+15C>T

gnomAD frequency: 0.43566  dbSNP: rs2075784

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423227	SCV000517989	benign	not specified	2015-11-02	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	RCV000423227	SCV000540086	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	RCV000587313	SCV000698681	benign	not provided	2016-05-24	criteria provided, single submitter	clinical testing	Variant summary: The POLE c.62+15C>T intronic variant involves the alteration of a non-conserved nucleotide. One in silico tool predicts a benign outcome for this variant along with 5/5 splice site tools predicitng the variant not to have an impact on splicing. This variant was found in 5171/10550 control chromosomes (1292 homozygotes) at a frequency of 0.4901422, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic POLE variant (0.0000142), suggesting this variant is likely a benign polymorphism. Taken together, this variant is classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV000423227	SCV000806828	benign	not specified	2016-10-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587313	SCV001470789	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000587313	SCV001716893	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789324	SCV002031661	benign	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789325	SCV002031662	benign	Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency	2021-10-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002356538	SCV002655060	benign	Hereditary cancer-predisposing syndrome	2015-05-19	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	RCV001509972	SCV004016688	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000587313	SCV005237716	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000423227	SCV001920212	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000423227	SCV001957086	benign	not specified		no assertion criteria provided	clinical testing