ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1500del (p.Val501fs)

dbSNP: rs759151952
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Department of Laboratory Medicine, University of Washington RCV000210104 SCV000266118 pathogenic Lynch syndrome 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000694702 SCV000823159 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-08-02 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: 224541). This premature translational stop signal has been observed in individual(s) with constitutional mismatch repair deficiency (CMMRD) and breast cancer (PMID: 26845104, 28381238). This variant is present in population databases (rs759151952, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Val501Trpfs*94) 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).
Ambry Genetics RCV001011895 SCV001172277 pathogenic Hereditary cancer-predisposing syndrome 2022-12-13 criteria provided, single submitter clinical testing The c.1500delC pathogenic mutation, located in coding exon 11 of the PMS2 gene, results from a deletion of one nucleotide at nucleotide position 1500, causing a translational frameshift with a predicted alternate stop codon (p.V501Wfs*94). This variant has been reported as a heterozygous variant in a Lynch syndrome family and a homozygous finding in an individual with constitutionl mismatch repair deficiency (CMMRD) (Shirts BH et al. Genet. Med., 2016 10;18:974-81; Ramchander NC et al. BMC Med. Genet., 2017 Apr;18:40). 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.
Myriad Genetics, Inc. RCV003454555 SCV004187788 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.

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