Submissions for variant NM_006231.4(POLE):c.4530A>G (p.Ala1510=)

gnomAD frequency: 0.53564  dbSNP: rs5744944

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000424670	SCV000517998	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000424670	SCV000540082	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
Ambry Genetics	RCV000492523	SCV000581370	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	RCV000589096	SCV000698676	benign	not provided	2016-05-19	criteria provided, single submitter	clinical testing	Variant summary: The POLE c.4530A>G (p.Ala1510Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 60324/119880 control chromosomes (15839 homozygotes) at a frequency of 0.5032032, which is approximately 35425 times 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	RCV000424670	SCV000806785	benign	not specified	2016-10-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589096	SCV001470785	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000589096	SCV001730162	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789332	SCV002031644	benign	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789333	SCV002031645	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	RCV001520942	SCV004016677	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589096	SCV005237223	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000424670	SCV001921959	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000424670	SCV001954988	benign	not specified		no assertion criteria provided	clinical testing