Submissions for variant NM_002691.4(POLD1):c.463+8_463+9delinsTT

dbSNP: rs796285537

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204810	SCV000262173	benign	Colorectal cancer, susceptibility to, 10	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000204810	SCV000488923	likely benign	Colorectal cancer, susceptibility to, 10	2016-07-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000481167	SCV000568181	likely benign	not specified	2016-09-12	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	RCV000590576	SCV000698010	likely benign	not provided	2016-08-26	criteria provided, single submitter	clinical testing	Variant summary: The POLD1 c.463+8_463+9delinsTT variant involves the alteration of non-conserved nucleotides, resulting in a intronic change. This delins variant is not found in ExAC; however, the individual variants that form the variant of interest, viz. 19:50905189 G / T and 19:50905190 C / T are found at allele frequencies of 0.1145 (13864/ 121128) and 0.007434 (901/121202), respectively. In African sub-population, they have allele frequencies of 0.2939 and 0.08015, respectively. Therefore, it is highly likely they are in a considerable linkage disequilibrium such that the variant of interest also has a frequency that exceeds the estimated maximal expected allele frequency (0.00142) based on the disease prevalence of CRC. One clinical lab in ClinVar has classified it bas benign. The variant of interest has not been reported in affected individuals via publications, to our knowledge. Taken together, this variant is classified as likely benign.
True Health Diagnostics	RCV000664286	SCV000788149	likely benign	Hereditary cancer-predisposing syndrome	2017-10-25	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358566	SCV001554342	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The POLD1 c.463+8_463+9delinsTT variant was not identified in the literature nor was it identified in MutDB. The variant was identified in dbSNP (ID: rs796285537 as With other allele) and ClinVar (3x as likely benign and 1x as benign). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). However, each nucleotide substitution included in this variant was identified in control databases: c.463+8G>T at a frequency of 0.1, c.463+9C>T at a frequency of 0.007, and both occurring at the highest frequency in the African population (Genome Aggregation Database Feb 27, 2017). In addition, the two variants are sometimes identified in both ExAC and Gnomad as occurring in cis (c.463+8_463+9delinsTT variant), which can be seen in the IGV tracks provided; however, frequency information is not available at this time. In summary, the clinical significance of this variant cannot be determined with certainty at this time, although available information suggests a benign role. This variant is classified as likely benign.