Submissions for variant NM_000535.6(PMS2):c.2182_2184delinsG (p.Thr728Alafs)

dbSNP: rs1554294508

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000213238	SCV000276014	pathogenic	Hereditary cancer-predisposing syndrome	2020-02-04	criteria provided, single submitter	clinical testing	The c.2182_2187delACTCTCinsGCTC pathogenic mutation (also known as p.T728Afs*7) , located in coding exon 13 of the PMS2 gene, results from the deletion of 6 nucleotides and insertion of 4 nucleotides at positions 2182 to 2187 causing a translational frameshift with a predicted alternate stop codon. This pathogenic mutation was reported in a female proband diagnosed with colorectal cancer at 51 years of age who met Amsterdam II criteria for Lynch syndrome (Guindalini RS et al. Gastroenterology, 2015 Nov;149:1446-53). In addition to the clinical data presented in the literature, 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	RCV000704156	SCV000833094	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2019-12-13	criteria provided, single submitter	clinical testing
Molecular Oncology Research Center, Barretos Cancer Hospital	RCV001374506	SCV001438599	pathogenic	Hereditary breast ovarian cancer syndrome	2020-08-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000213238	SCV002530270	likely pathogenic	Hereditary cancer-predisposing syndrome	2021-04-23	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV003454639	SCV004188575	pathogenic	Lynch syndrome 4	2023-09-22	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.