Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000202855 | SCV000257855 | benign | not specified | 2015-07-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000206033 | SCV000261396 | benign | Colorectal cancer, susceptibility to, 10 | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000206033 | SCV000489206 | likely benign | Colorectal cancer, susceptibility to, 10 | 2016-09-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000202855 | SCV000520746 | likely benign | not specified | 2017-12-20 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Ambry Genetics | RCV000570573 | SCV000670910 | likely benign | Hereditary cancer-predisposing syndrome | 2018-06-28 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589356 | SCV000697995 | benign | not provided | 2017-08-09 | criteria provided, single submitter | clinical testing | Variant summary: The POLD1 c.2007-4G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 151/120110 control chromosomes (1 homozygote) at a frequency of 0.0012572, which is approximately 89 times the estimated maximal expected allele frequency of a pathogenic POLD1 variant (0.0000142), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000202855 | SCV000888446 | benign | not specified | 2018-04-27 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000206033 | SCV001141150 | likely benign | Colorectal cancer, susceptibility to, 10 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000589356 | SCV001502264 | likely benign | not provided | 2024-08-01 | criteria provided, single submitter | clinical testing | POLD1: BP4, BS1 |
ARUP Laboratories, |
RCV000589356 | SCV002047969 | benign | not provided | 2022-09-16 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000202855 | SCV002065992 | benign | not specified | 2017-08-29 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000570573 | SCV002534615 | benign | Hereditary cancer-predisposing syndrome | 2020-07-28 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000202855 | SCV002551944 | likely benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004737322 | SCV000806483 | likely benign | POLD1-related disorder | 2024-05-01 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Department of Pathology and Laboratory Medicine, |
RCV001357515 | SCV001553005 | likely benign | Carcinoma of colon | no assertion criteria provided | clinical testing | The POLD1 c.2007-4G>A variant was not identified in the literature nor was it identified in the Cosmic database. The variant was identified in dbSNP (ID: rs202035484 as "With Likely benign, Uncertain significance, other allele"), ClinVar (3x as benign by Invitae, and two other clinical laboratories and 4x as likely benign by Counsyl, GeneDx, Ambry Genetics and one other clinical laboratory), and in LOVD 3.0 (2x as benign). The variant was identified in control databases in 346 of 275244 chromosomes (1 homozygous) at a frequency of 0.001, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 9 of 23976 chromosomes (freq: 0.0004), Other in 5 of 6442 chromosomes (freq: 0.0008), Latino in 37 of 34414 chromosomes (freq: 0.001), European in 237 of 124870 chromosomes (freq: 0.002), Ashkenazi Jewish in 2 of 10138 chromosomes (freq: 0.0002), Finnish in 48 of 25786 chromosomes (freq: 0.002), and South Asian in 8 of 30782 chromosomes (freq: 0.0003); it was not observed in the East Asian population. 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. | |
Genome Diagnostics Laboratory, |
RCV000202855 | SCV001807599 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000202855 | SCV001918170 | benign | not specified | no assertion criteria provided | clinical testing |