Submissions for variant NM_002691.4(POLD1):c.2953+12C>T

gnomAD frequency: 0.55791  dbSNP: rs3218776

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000244063	SCV000309126	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000244063	SCV000517988	benign	not specified	2015-11-02	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000244063	SCV000540077	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587096	SCV000698002	benign	not provided	2016-05-19	criteria provided, single submitter	clinical testing	Variant summary: The POLD1 c.2953+12C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant, and 5/5 Alamut algorithms predict not significant change to splicing. This variant was found in 13998/24162 control chromosomes (4157 homozygotes) at a frequency of 0.5793395, which is approximately 40785 times the estimated maximal expected allele frequency of a pathogenic POLD1 variant (0.0000142), highly suggesting this variant is a benign polymorphism. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587096	SCV001472301	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001516689	SCV001725002	benign	Colorectal cancer, susceptibility to, 10	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789278	SCV002031626	benign	Mandibular hypoplasia-deafness-progeroid syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436083	SCV002749080	benign	Hereditary cancer-predisposing syndrome	2015-05-21	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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001516689	SCV004016609	benign	Colorectal cancer, susceptibility to, 10	2023-07-07	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000244063	SCV004232987	benign	not specified	2024-01-24	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV000587096	SCV005309877	benign	not provided		criteria provided, single submitter	not provided