ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.223del (p.Gly74_Val75insTer)

dbSNP: rs1554304974
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000551564 SCV000625602 pathogenic Hereditary nonpolyposis colorectal neoplasms 2017-04-22 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 3 of the PMS2 mRNA (c.223delG), causing a frameshift at codon 75. This creates a premature translational stop signal (p.Val75*) and is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816).
Color Diagnostics, LLC DBA Color Health RCV000771715 SCV000904351 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 3 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 RCV000771715 SCV002726877 pathogenic Hereditary cancer-predisposing syndrome 2018-10-01 criteria provided, single submitter clinical testing The c.223delG pathogenic mutation, located in coding exon 3 of the PMS2 gene, results from a deletion of one nucleotide at nucleotide position 223, causing a translational frameshift with a predicted alternate stop codon (p.V75*). 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. RCV003449546 SCV004187701 pathogenic Lynch syndrome 4 2023-09-18 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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