Submissions for variant NM_002691.4(POLD1):c.463+8G>T

gnomAD frequency: 0.13898  dbSNP: rs1726802

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000411960	SCV000488930	likely benign	Colorectal cancer, susceptibility to, 10	2016-07-20	criteria provided, single submitter	clinical testing
GeneDx	RCV000434530	SCV000518016	benign	not specified	2015-11-06	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587348	SCV000698011	benign	not provided	2016-05-18	criteria provided, single submitter	clinical testing	Variant summary: The POLD1 c.463+8G>T variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing, although these predictions have yet to be functionally assessed. This variant was observed in the large, broad control population, ExAC, with an allele frequency of 13864/121128 (1142 homozygotes, 1/8, frequency: 0.1144574), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic POLD1 variant of 1/70422 (0.0000142), suggesting this variant is likely 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. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV000434530	SCV000806543	benign	not specified	2016-11-02	criteria provided, single submitter	clinical testing
Invitae	RCV000411960	SCV001725774	benign	Colorectal cancer, susceptibility to, 10	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001789323	SCV002031623	benign	Mandibular hypoplasia-deafness-progeroid syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002338968	SCV002635239	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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000411960	SCV004016612	benign	Colorectal cancer, susceptibility to, 10	2023-07-07	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000434530	SCV004232814	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 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported.