Submissions for variant NM_002691.4(POLD1):c.234C>G (p.Arg78=)

gnomAD frequency: 0.03571  dbSNP: rs2228665

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000444537	SCV000518890	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084356	SCV000558700	benign	Colorectal cancer, susceptibility to, 10	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567046	SCV000670872	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: 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, LabCorp	RCV000590144	SCV000697998	benign	not provided	2016-05-17	criteria provided, single submitter	clinical testing	Variant summary: The POLD1 c.234C>G (p.Arg78Arg) 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. 4/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 1258/120890 control chromosomes (73 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.1125917 (1166/10356). This frequency is about 7926 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 African origin. 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.
PreventionGenetics, part of Exact Sciences	RCV000444537	SCV000806499	benign	not specified	2016-12-06	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000444537	SCV000889662	benign	not specified	2016-08-04	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000444537	SCV002761042	benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001084356	SCV004016622	benign	Colorectal cancer, susceptibility to, 10	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590144	SCV005309837	benign	not provided		criteria provided, single submitter	not provided
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000567046	SCV005688951	benign	Hereditary cancer-predisposing syndrome	2025-01-20	criteria provided, single submitter	clinical testing	The synonymous variant NM_001308632.1(POLD1):c.234C>G (p.Arg78=) has been reported to ClinVar as Benign with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 380633 as of 2025-01-02). The variant is observed in one or more well-documented healthy adults.The p.Arg78= variant is observed in 177/5,008 (3.5343%) alleles from individuals of 1kG All background in 1kG, indicating it is a common benign variant. The p.Arg78= variant is not predicted to disrupt an existing splice site. The p.Arg78= variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Benign.
True Health Diagnostics	RCV000567046	SCV000788140	likely benign	Hereditary cancer-predisposing syndrome	2017-10-25	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354218	SCV001548775	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The POLD1 p.Arg78= variant was identified in dbSNP (ID: rs2228665) “With Benign allele”, ClinVar (classified benign by GeneDx, Invitae, Ambry Genetics and Quest Diagnostics Nichols Institute San Juan Capistrano), and in control databases in 3050 (173 homozygous) of 277140 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 2735 (171 homozygous) of 24022 chromosomes (freq: 0.11), Other in 27 of 6466 chromosomes (freq: 0.004), Latino in 253 (2 homozygous) of 34418 chromosomes (freq: 0.007), European Non-Finnish in 32 of 126664 chromosomes (freq: 0.0003), Ashkenazi Jewish in 1 of 10150 chromosomes (freq: 0.0001), and South Asian in 2 of 30782 chromosomes (freq: 0.00007), while not observed in the East Asian and European Finnish populations. The p.Arg78= 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 summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000444537	SCV001807753	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000444537	SCV001925488	benign	not specified		no assertion criteria provided	clinical testing