ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1714_1717delinsACAT (p.Ala572_Thr573delinsThrSer) (rs1060503126)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460576 SCV000551981 uncertain significance Lynch syndrome 2016-11-10 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides and inserts 4 new nucleotides in exon 11 of the PMS2 mRNA (c.1714_1717delinsACAT). This replaces 2 amino acid residues in the PMS2 protein (p.Ala572_Thr573delinsThrSer) but otherwise preserves the integrity of the reading frame. While this variant, as described in this report, is not present in population databases, two variants in phase, c.1714G>A (p.Ala572Thr) and c.1717A>T (p.Thr573Ser) are present in population databases (rs63751023 and rs63751211). It has not been reported in the literature in individuals with a PMS2-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the replaced amino acids is currently unknown. In summary, this is a rare variant with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000484542 SCV000565417 uncertain significance not provided 2018-05-03 criteria provided, single submitter clinical testing This combined deletion and insertion of four nucleotides in PMS2 is denoted c.1714_1717delGCAAinsACAT at the cDNA level and p.Ala572_Thr573delinsThrSer at the protein level. The surrounding sequence is TCTC[delGCAA][insACAT]CCCCA. The deletion and insertion results in the replacement of an Alanine and Threonine with a Threonine and Serine, creating two adjacent missense changes: Ala572Thr and Thr573Ser. This combined variant was reported in an individual undergoing multigene cancer panel testing due to a history of a Lynch-related cancer and/or polyps (Yurgelun 2015). PMS2 Ala572_Thr573delinsThrSer was not observed in large population cohorts, and although PMS2 Ala572Thr and Thr573Ser were each individually observed, population data in this region of PMS2 are not considered reliable due to high pseudogene homology (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether PMS2 Ala572_Thr573delinsThrSer is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.