ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2142G>A (p.Leu714=)

gnomAD frequency: 0.00001  dbSNP: rs1060501816
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000468448 SCV000547539 uncertain significance Colorectal cancer, susceptibility to, 10 2025-01-17 criteria provided, single submitter clinical testing This sequence change affects codon 714 of the POLD1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the POLD1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 24 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 407992). Studies have shown this variant is associated with an activation of a cryptic splice site in exon 17, but one or more of the resulting mRNA isoform(s) may be naturally occurring (internal data). 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.
Ambry Genetics RCV002429502 SCV002730279 likely benign Hereditary cancer-predisposing syndrome 2020-07-07 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.
Fulgent Genetics, Fulgent Genetics RCV002481429 SCV002782818 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2021-10-07 criteria provided, single submitter clinical testing

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