Submissions for variant NM_000535.7(PMS2):c.1196dup (p.Gln400fs)

dbSNP: rs1554298056

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000571044	SCV000670764	pathogenic	Hereditary cancer-predisposing syndrome	2018-04-18	criteria provided, single submitter	clinical testing	The c.1196dupA pathogenic mutation, located in coding exon 11 of the PMS2 gene, results from a duplication of A at nucleotide position 1196, causing a translational frameshift with a predicted alternate stop codon (p.K399Kfs*59). 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.
Invitae	RCV001386454	SCV001586684	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2023-08-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 484257). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln400Alafs*58) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816).
Color Diagnostics, LLC DBA Color Health	RCV000571044	SCV001735156	pathogenic	Hereditary cancer-predisposing syndrome	2023-03-29	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 11 of the PMS2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002476241	SCV002774373	pathogenic	not provided	2021-06-23	criteria provided, single submitter	clinical testing	This frameshift variant causes the premature termination of PMS2 protein synthesis. To the best of our knowledge, the variant has not been reported in individuals with PMS2-related conditions in the published literature. Based on the available information, this variant is classified as pathogenic.
Myriad Genetics, Inc.	RCV003451262	SCV004188611	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.
All of Us Research Program, National Institutes of Health	RCV004001070	SCV004839836	pathogenic	Lynch syndrome	2023-06-08	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 11 of the PMS2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.