ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2243_2246del (p.Lys748fs)

dbSNP: rs267608173
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076848 SCV000108337 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Counsyl RCV000409351 SCV000488736 pathogenic Lynch syndrome 4 2016-06-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575018 SCV000674233 pathogenic Hereditary cancer-predisposing syndrome 2023-08-30 criteria provided, single submitter clinical testing The c.2243_2246delAGAA pathogenic mutation, located in coding exon 13 of the PMS2 gene, results from a deletion of 4 nucleotides at nucleotide positions 2243 to 2246, causing a translational frameshift with a predicted alternate stop codon (p.K748Mfs*19). This mutation (also designated as 2267delAGAA) has been reported in at least one individual diagnosed with colon cancer before age 40 (Jenkins MA et al. Clin. Gastroenterol. Hepatol., 2006 Apr;4:489-98; Southey MC et al. J. Clin. Oncol., 2005 Sep;23:6524-32). 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 RCV001239541 SCV001412420 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-08 criteria provided, single submitter clinical testing The location of this variant in this individual is uncertain. It could create a nonsense change (c.2243_2246del, p.Lys748Metfs*19) in exon 13 of the PMS2 gene, or a variant in exon 4 of the PMS2CL pseudogene. Until the location of this sequence change can be resolved, the clinical significance of this variant remains uncertain. It has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002498371 SCV002806527 pathogenic Lynch syndrome 4; Mismatch repair cancer syndrome 4 2022-04-16 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000409351 SCV004019949 pathogenic Lynch syndrome 4 2023-04-05 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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