Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000230988 | SCV000287504 | likely benign | Colorectal cancer, susceptibility to, 10 | 2025-01-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000576089 | SCV000674276 | likely benign | Hereditary cancer-predisposing syndrome | 2024-03-07 | 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. |
| Gene |
RCV001722232 | SCV000725642 | likely benign | not provided | 2020-09-08 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV003493537 | SCV004242980 | likely benign | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001356777 | SCV001552037 | uncertain significance | Carcinoma of colon | no assertion criteria provided | clinical testing | The POLD1 c.1138-3C>T variant was not identified in the literature. The variant was identified in dbSNP (rs200072694) as “with uncertain significance allele” and ClinVar (classified as likely benign by Invitae and GeneDx and uncertain significance by Ambry Genetics). The variant was identified in control databases in 27 of 282,630 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 22 of 19,952 chromosomes (freq: 0.001), South Asian in 5 of 30,614 chromosomes (freq: 0.0002), while the variant was not observed in the African, Latino, Ashkenazi Jewish, Finnish, European and Other populations. The c.1138-3C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. Further, 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |