Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000205810 | SCV000261969 | benign | Colorectal cancer, susceptibility to, 10 | 2024-02-01 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000205810 | SCV000489056 | likely benign | Colorectal cancer, susceptibility to, 10 | 2016-08-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001722134 | SCV000568173 | likely benign | not provided | 2020-03-12 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000483226 | SCV000918076 | benign | not specified | 2018-08-27 | criteria provided, single submitter | clinical testing | Variant summary: POLD1 c.3218+9_3218+10delinsTG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was inferred to be at a frequency of 0.0052 in 226738 control chromosomes in the gnomAD database, including 10 homozygotes. The observed variant frequency is approximately 368-fold of the estimated maximal expected allele frequency for a pathogenic variant in POLD1 causing Colorectal Cancer phenotype (1.4e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3218+9_3218+10delinsTG in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. All laboratories classified the variant as benign/likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001722134 | SCV004219065 | benign | not provided | 2023-02-20 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001358426 | SCV001554154 | likely benign | Carcinoma of colon | no assertion criteria provided | clinical testing | The POLD1 c.3218+9_3218+10delinsTG variant was not identified in the literature nor was it identified in the ClinVar database. The variant was only identified in dbSNP (ID: rs386810227) as "With other allele". The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). However, the POLD1 c.3218+9C>T variant was identified in control databases in 1197 of 231534 chromosomes (10 homozygous) at a frequency of 0.005 and the POLD1 c.3218+10A>G variant was identified in control databases in 10250 of 231916 chromosomes (1374 homozygous) at a frequency of 0.04 (Genome Aggregation Database Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do 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. |