Submissions for variant NM_000535.7(PMS2):c.1687_1693del (p.Arg563fs)

dbSNP: rs1064795345

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484807	SCV000571056	pathogenic	not provided	2016-07-25	criteria provided, single submitter	clinical testing	This deletion of seven nucleotides in PMS2 is denoted c.1687_1693delCGAGTTT at the cDNA level and p.Arg563CysfsX30 (R563CfsX30) at the protein level. The normal sequence, with the bases that are deleted in braces, is ATTT[CGAGTTT]TGCC. The deletion causes a frameshift which changes an Arginine to a Cysteine at codon 563, and creates a premature stop codon at position 30 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Ambry Genetics	RCV002402409	SCV002710766	pathogenic	Hereditary cancer-predisposing syndrome	2021-05-17	criteria provided, single submitter	clinical testing	The c.1687_1693delCGAGTTT pathogenic mutation, located in coding exon 11 of the PMS2 gene, results from a deletion of 7 nucleotides at nucleotide positions 1687 to 1693, causing a translational frameshift with a predicted alternate stop codon (p.R563Cfs*30). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV003449219	SCV004188666	pathogenic	Lynch syndrome 4	2023-09-20	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.