ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.433G>A (p.Ala145Thr) (rs137953986)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573522 SCV000670893 likely benign Hereditary cancer-predisposing syndrome 2015-06-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,In silico models in agreement (benign)
CSER_CC_NCGL; University of Washington Medical Center RCV000417237 SCV000503557 likely benign Colon cancer 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 47 year old with a history of colon cancer diagnosed at 47 and a family history of colon cancer. In exonuclease domain.
GeneDx RCV000236076 SCV000293557 likely benign not specified 2017-12-22 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.
Integrated Genetics/Laboratory Corporation of America RCV000588877 SCV000698009 likely benign not provided 2016-08-26 criteria provided, single submitter clinical testing Variant summary: The POLD1 c.433G>A (p.Ala145Thr) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant is located in the Ribonuclease H-like domain (InterPro).This variant was found in 308/121298 control chromosomes (2 homozygotes), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.012269 (81/6602). This frequency is about 864 times the estimated maximal expected allele frequency of a pathogenic POLD1 variant (0.0000142), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. In a non-peer reviewed project report this variant was reported to be found in 3/95 CRC patients (Rypdal KB, 2015). Another missense change at the same residue p.A145D has also been found in one CRC patient who did not have somatic pathogenic variants (PMID 23263490). Although it is not monogenically linked to CRC phenotype based on population data, whether this variant represents a risk allele needs to be further examined by case-control studies. There are no published functional studies. In ClinVar, while one clinical lab classifies it as uncertain significance, another as benign. Taken together, this variant is currently classified as likely benign.
Invitae RCV000204920 SCV000262343 benign Colorectal cancer 10 2018-01-04 criteria provided, single submitter clinical testing
PreventionGenetics RCV000588877 SCV000806540 likely benign not provided 2017-03-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236076 SCV000601943 likely benign not specified 2017-02-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588877 SCV000889688 benign not provided 2018-02-09 criteria provided, single submitter clinical testing

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