Submissions for variant NM_000535.7(PMS2):c.269_270dup (p.Lys91fs)

dbSNP: rs1554304745

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000663233	SCV000786435	likely pathogenic	Lynch syndrome 4	2018-04-29	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985908	SCV001134598	likely pathogenic	not provided	2019-02-03	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Not found in the gnomAD exomes dataset, and the data is high quality (0/242162 chr).
Invitae	RCV001064263	SCV001229152	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2021-08-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys91Leufs*9) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 548899). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV001177939	SCV001342255	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant inserts 2 nucleotides in exon 4 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. 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.
Ambry Genetics	RCV001177939	SCV002745324	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-01	criteria provided, single submitter	clinical testing	The c.269_270dupCT pathogenic mutation, located in coding exon 4 of the PMS2 gene, results from a duplication of CT at nucleotide position 269, causing a translational frameshift with a predicted alternate stop codon (p.K91Lfs*9). 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.	RCV000663233	SCV004019770	pathogenic	Lynch syndrome 4	2023-04-03	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.