ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.846C>T (p.Pro282=)

gnomAD frequency: 0.00291  dbSNP: rs5744758
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000232551 SCV000289497 benign not provided 2025-02-03 criteria provided, single submitter clinical testing
GeneDx RCV000232551 SCV000518908 benign not provided 2019-03-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000232551 SCV000602101 benign not provided 2023-06-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570065 SCV000671273 benign Hereditary cancer-predisposing syndrome 2015-08-22 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.
PreventionGenetics, part of Exact Sciences RCV000423707 SCV000806857 benign not specified 2018-01-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000423707 SCV000920071 benign not specified 2018-01-08 criteria provided, single submitter clinical testing Variant summary: The POLE c.846C>T (p.Pro282Pro) variant involves the alteration of a non-conserved nucleotide located in the DNA-directed DNA polymerase, family B, exonuclease domain (IPR006133) (InterPro), resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. This variant was found in 282/277164 control chromosomes (2 homozygotes) in gnomAD at a frequency of 0.0010174, which is approximately 72 times the estimated maximal expected allele frequency of a pathogenic POLE variant (0.0000142), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Genetic Services Laboratory, University of Chicago RCV000423707 SCV002071594 benign not specified 2018-05-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002503914 SCV002811230 likely benign Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 2021-07-14 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV001079650 SCV004017090 benign Colorectal cancer, susceptibility to, 12 2023-07-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000232551 SCV005435810 likely benign not provided 2024-11-01 criteria provided, single submitter clinical testing POLE: BP4, BP7, BS1
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000570065 SCV005688849 benign Hereditary cancer-predisposing syndrome 2025-01-27 criteria provided, single submitter clinical testing The synonymous variant NM_006231.4(POLE):c.846C>T (p.Pro282=) has been reported to ClinVar as Benign/Likely benign with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 240632 as of 2025-01-02). . The p.Pro282= variant is observed in 18/5,008 (0.3594%) alleles from individuals of 1kG All background in 1kG, which is greater than expected for the disorder. The p.Pro282= variant is not predicted to disrupt an existing splice site. The p.Pro282= variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Benign.
True Health Diagnostics RCV000570065 SCV000886717 likely benign Hereditary cancer-predisposing syndrome 2018-10-04 no assertion criteria provided clinical testing

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