ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.758+5G>A (rs760003191)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227281 SCV000287649 uncertain significance Colorectal cancer 10 2018-12-13 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the POLD1 gene. It does not directly change the encoded amino acid sequence of the POLD1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs760003191, ExAC 0.01%). This variant has not been reported in the literature in individuals with POLD1-related disease. ClinVar contains an entry for this variant (Variation ID: 239367). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000826021 SCV000967510 uncertain significance not specified 2018-10-19 criteria provided, single submitter clinical testing The c.758+5G>A variant in POLD1 has not been previously reported in the literatu re in individuals with hereditary colorectal cancer but has been reported by oth er clinical laboratories in ClinVar (Variation ID: 239367). It has also been ide ntified in 3/23884 African chromosomes by gnomAD (http://gnomad.broadinstitute.o rg). This variant is located in the 5' splice region. Computational tools sugges t a possible impact to splicing. However, this information is not predictive eno ugh to determine pathogenicity. In summary, the clinical significance of the c.7 58+5G>A variant is uncertain. ACMG/AMP Criteria applied: PP3.
PreventionGenetics RCV000679525 SCV000806555 uncertain significance not provided 2017-10-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679525 SCV000888479 uncertain significance not provided 2018-05-04 criteria provided, single submitter clinical testing

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