Submissions for variant NM_002691.4(POLD1):c.2612_2623del (p.Leu871_Asn874del)

dbSNP: rs1064792943

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000456614	SCV000547489	uncertain significance	Colorectal cancer, susceptibility to, 10	2020-09-01	criteria provided, single submitter	clinical testing	In summary, this variant is a novel in-frame deletion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Experimental studies have not been published for this variant and the functional importance of the deleted amino acids is not known. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a POLD1-related disease. This sequence change deletes 12 nucleotides from exon 21 of the POLD1 mRNA (c.2612_2623delTGCTGTGCAACC). This leads to the deletion of 4 amino acid residue(s) in the POLD1 protein (p.Leu871_Asn874del) but otherwise preserves the integrity of the reading frame.
Ambry Genetics	RCV002436416	SCV002745245	uncertain significance	Hereditary cancer-predisposing syndrome	2020-06-25	criteria provided, single submitter	clinical testing	The c.2612_2623del12 variant (also known as p.L871_N874del) is located in coding exon 20 of the POLD1 gene. This variant results from an in-frame deletion of 12 nucleotides at positions 2612 to 2623. This results in the in-frame deletion of 4 amino acid residues at codons 871 to 874. This amino acid region is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV003236802	SCV003935768	uncertain significance	not provided	2022-12-21	criteria provided, single submitter	clinical testing	In-frame deletion of 4 amino acids in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge