Submissions for variant NM_006231.4(POLE):c.6252A>G (p.Ser2084=)

gnomAD frequency: 0.66039  dbSNP: rs5745022

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000427516	SCV000518001	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.
Ambry Genetics	RCV000492779	SCV000581371	benign	Hereditary cancer-predisposing syndrome	2015-05-20	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589308	SCV000698682	benign	not provided	2016-08-17	criteria provided, single submitter	clinical testing	Variant summary: The c.6252G>A (p.Ser2084=) in POLE gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.638 (77431/1211338 chrs tested) including numerous homozygous occurrences. The variant of interest has not, to our knowledge, been reported in affected individuals or cited by reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000427516	SCV000711959	benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: Frequency
PreventionGenetics, part of Exact Sciences	RCV000427516	SCV000806829	benign	not specified	2016-10-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000589308	SCV001000927	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589308	SCV001470787	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789336	SCV002031635	benign	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789337	SCV002031636	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	RCV001080796	SCV004016674	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589308	SCV005237204	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000427516	SCV001918317	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000427516	SCV001956743	benign	not specified		no assertion criteria provided	clinical testing