Submissions for variant NM_000535.7(PMS2):c.33del (p.Ala12fs)

dbSNP: rs1554306605

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657458	SCV000779193	pathogenic	not provided	2018-02-02	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in PMS2 is denoted c.33delT at the cDNA level and p.Ala12LeufsX22 (A12LfsX22) at the protein level. The normal sequence, with the base that is deleted in brackets, is AACC[delT]GCTA. The deletion causes a frameshift which changes an Alanine to a Leucine at codon 12, and creates a premature stop codon at position 22 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.
Color Diagnostics, LLC DBA Color Health	RCV000772968	SCV000906350	pathogenic	Hereditary cancer-predisposing syndrome	2020-06-11	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 2 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.
Myriad Genetics, Inc.	RCV003451597	SCV004188675	pathogenic	Lynch syndrome 4	2023-09-18	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.