Submissions for variant NM_006231.4(POLE):c.2320-13A>G

gnomAD frequency: 0.01853  dbSNP: rs75329753

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000434941	SCV000518045	benign	not specified	2015-11-12	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	RCV000588219	SCV000698664	benign	not provided	2016-05-24	criteria provided, single submitter	clinical testing	Variant summary: The POLE c.2320-13A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 723/118988 control chromosomes (15 homozygotes) at a frequency of 0.0060762, which is approximately 428 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	RCV000434941	SCV000806742	benign	not specified	2016-11-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588219	SCV001472367	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000588219	SCV001724685	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000434941	SCV002550149	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002450975	SCV002735699	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	RCV001516412	SCV004016718	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588219	SCV005237693	benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357090	SCV001552437	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The POLE c.2320-13A>G variant was identified in dbSNP (ID: rs75329753) “With Benign allele”, and ClinVar (classified benign by GeneDx and 2 other laboratories). The variant was identified in control databases in 1761 (45 homozygous) of 272276 chromosomes at a frequency of 0.006 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1411 (43 homozygous) of 23996 chromosomes (freq: 0.06), Other in 34 of 6412 chromosomes (freq: 0.005), Latino in 144 (2 homozygous) of 34316 chromosomes (freq: 0.004), European Non-Finnish in 67 of 125992 chromosomes (freq: 0.0005), Ashkenazi Jewish in 95 of 10114 chromosomes (freq: 0.009), and South Asian in 10 of 30724 chromosomes (freq: 0.0003) while not observed in the East Asian and European Finnish populations. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000434941	SCV001809760	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000434941	SCV001917479	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000434941	SCV001952444	benign	not specified		no assertion criteria provided	clinical testing