Submissions for variant NM_006231.4(POLE):c.6004+5G>T

gnomAD frequency: 0.00014  dbSNP: rs372169366

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001705177	SCV000261529	benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001705177	SCV000567812	likely benign	not provided	2020-06-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000573861	SCV000671288	likely benign	Hereditary cancer-predisposing syndrome	2018-12-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000482029	SCV000712556	uncertain significance	not specified	2016-11-15	criteria provided, single submitter	clinical testing	The c.6004+5G>T variant in POLE has not been previously reported in individuals with colorectal cancer but has been identified in 22/65018 of European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs372169366). This variant is located in the 5' splice region. Although nucl eotide substitutions at +5 position of the intron are relatively common causes o f aberrant splicing, computational tools do not suggest an impact to splicing. H owever, this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the c.6004+5G>T variant is uncertain.
Counsyl	RCV000206794	SCV000786181	uncertain significance	Colorectal cancer, susceptibility to, 12	2018-03-13	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000482029	SCV001470076	benign	not specified	2019-12-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000482029	SCV002065138	benign	not specified	2021-06-17	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000573861	SCV002536905	likely benign	Hereditary cancer-predisposing syndrome	2021-07-29	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000482029	SCV002550047	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
True Health Diagnostics	RCV000573861	SCV000886715	likely benign	Hereditary cancer-predisposing syndrome	2018-07-11	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530237	SCV004720619	likely benign	POLE-related disorder	2019-04-24	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).