Submissions for variant NM_002691.4(POLD1):c.1485C>T (p.Thr495=)

gnomAD frequency: 0.09780  dbSNP: rs2230245

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000254099	SCV000309125	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000254099	SCV000517987	benign	not specified	2015-10-29	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	RCV000573764	SCV000670870	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	RCV000590679	SCV000697990	benign	not provided	2016-08-25	criteria provided, single submitter	clinical testing	Variant summary: The c.1485C>T (p.Thr495=) in POLD1 gene is a synonymous change that involves a non-conserved nucleotide. 2/5 programs in Alamut predict that this variant may affect the normal splicing pattern by weakening the neighboring donor site, however no functional studies supporting these predictions were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.124 (5844/47134 chrs tested), including numerous homozygous occurrences. This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0000142). The variant of interest has not, to our knowledge, been reported in publications or cited by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084451	SCV001000947	benign	Colorectal cancer, susceptibility to, 10	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789277	SCV002031624	benign	Mandibular hypoplasia-deafness-progeroid syndrome	2021-10-25	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001084451	SCV004016607	benign	Colorectal cancer, susceptibility to, 10	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590679	SCV005309856	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000254099	SCV001918430	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000254099	SCV001959185	benign	not specified		no assertion criteria provided	clinical testing