Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000480581 | SCV000571098 | uncertain significance | not provided | 2016-07-25 | criteria provided, single submitter | clinical testing | This variant is denoted POLD1 c.2717+4C>T or IVS21+4C>T and consists of a C>T nucleotide substitution at the +4 position of intron 21 of the POLD1 gene. POLD1 c.2717+4C>T was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. The cytosine (C) nucleotide that is altered is not conserved across species. In silico models are inconclusive with respect to splicing, and in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available information, it is unclear whether POLD1 c.2717+4C>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000562043 | SCV000676193 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-07 | criteria provided, single submitter | clinical testing | The c.2717+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 20 in the POLD1 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000799530 | SCV000939198 | likely benign | Colorectal cancer, susceptibility to, 10 | 2024-01-27 | criteria provided, single submitter | clinical testing |