Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000427134 | SCV000518894 | benign | not specified | 2015-11-13 | 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. |
Invitae | RCV000459453 | SCV000558778 | benign | Colorectal cancer, susceptibility to, 10 | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000569706 | SCV000670878 | benign | Hereditary cancer-predisposing syndrome | 2015-05-20 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: 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, |
RCV000589154 | SCV000697992 | benign | not provided | 2016-05-19 | criteria provided, single submitter | clinical testing | Variant summary: The POLD1 c.1548C>T (p.Ala516Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect any ESE site. This variant was found in 1638/120504 control chromosomes (117 homozygotes) at a frequency of 0.0135929, which is approximately 957 times the estimated maximal expected allele frequency of a pathogenic POLD1 variant (0.0000142), suggesting this variant is likely a benign polymorphism. Taken together, this variant is classified as benign. |
Preventiongenetics, |
RCV000427134 | SCV000806467 | benign | not specified | 2016-12-06 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000427134 | SCV000889650 | benign | not specified | 2020-08-10 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000427134 | SCV002551918 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV000459453 | SCV004016627 | benign | Colorectal cancer, susceptibility to, 10 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
True Health Diagnostics | RCV000569706 | SCV000788129 | likely benign | Hereditary cancer-predisposing syndrome | 2017-10-25 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001354613 | SCV001549270 | benign | Carcinoma of colon | no assertion criteria provided | clinical testing | The POLD1 p.Ala516= variant was identified in dbSNP (ID: rs2230247) “With Benign allele”, ClinVar (classified benign by GeneDx, Invitae, Ambry Genetics and Quest Diagnostics Nichols Institute San Juan Capistrano), and in control databases in 3896 (256 homozygous) of 276142 chromosomes at a frequency of 0.01 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3408 (250 homozygous) of 23952 chromosomes (freq: 0.14), Other in 42 of 6448 chromosomes (freq: 0.007), Latino in 328 (5 homozygous) of 34418 chromosomes (freq: 0.01), European Non-Finnish in 77 (1 homozygous) of 125860 chromosomes (freq: 0.0006), Ashkenazi Jewish in 32 of 10134 chromosomes (freq: 0.003), and South Asian in 9 of 30778 chromosomes (freq: 0.0003), while not observed in the East Asian and European Finnish populations. The p.Ala516= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. | |
Genome Diagnostics Laboratory, |
RCV000427134 | SCV001809249 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000427134 | SCV001922862 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000427134 | SCV001951120 | benign | not specified | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000427134 | SCV002036976 | benign | not specified | no assertion criteria provided | clinical testing |