ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3378+7G>T

gnomAD frequency: 0.00008  dbSNP: rs755370377
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000759287 SCV000289329 benign not provided 2024-01-29 criteria provided, single submitter clinical testing
Counsyl RCV000226840 SCV000489720 likely benign Colorectal cancer, susceptibility to, 12 2016-11-10 criteria provided, single submitter clinical testing
GeneDx RCV000603287 SCV000713986 likely benign not specified 2017-10-25 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759287 SCV000888526 benign not provided 2018-04-26 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002258852 SCV002536811 benign Hereditary cancer-predisposing syndrome 2021-01-07 criteria provided, single submitter curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000226840 SCV004017062 benign Colorectal cancer, susceptibility to, 12 2023-07-07 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000603287 SCV004027333 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004541431 SCV004759785 likely benign POLE-related disorder 2020-01-13 criteria provided, single submitter 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).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001356287 SCV001551414 likely benign Familial ovarian cancer no assertion criteria provided clinical testing The POLE c.3378+7G>T variant was not identified in the literature. The variant was identified in dbSNP (rs755370377) as “with other allele” and ClinVar (interpreted as "benign" by Invitae and Quest Diagnostics and "likely benign" by GeneDx and Counsyl). The variant was identified in control databases in 30 of 277,184 chromosomes at a frequency of 0.0001 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: European in 4 of 126,694 chromosomes (freq: 0.00003), Ashkenazi Jewish in 25 of 10,150 chromosomes (freq: 0.002), and South Asian in 1 of 30,778 chromosomes (freq: 0.00003). The variant was not observed in the African, Other, Latino, East Asian and Finnish populations. The variant occurs at a non-conserved nucleotide outside of the consensus splicing sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) did not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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