ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.347_350del (p.Asp116fs)

dbSNP: rs63750501
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076569 SCV000107600 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269636 SCV001449761 pathogenic not provided 2019-10-30 criteria provided, single submitter clinical testing
Invitae RCV001390797 SCV001592644 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-03-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with Lynch syndrome (PMID: 17389002). ClinVar contains an entry for this variant (Variation ID: 91067). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp116Glyfs*57) in the MSH2 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002453389 SCV002613938 pathogenic Hereditary cancer-predisposing syndrome 2019-08-20 criteria provided, single submitter clinical testing The c.347_350delATTG pathogenic mutation, located in coding exon 2 of the MSH2 gene, results from a deletion of 4 nucleotides at nucleotide positions 347 to 350, causing a translational frameshift with a predicted alternate stop codon (p.D116Gfs*57). This variant has been reported in an individual diagnosed with anaplastic astrocytoma exhibiting loss of MSH2 protein by immunohistochemistry at age 45 and with a family history of early onset colorectal cancer and kidney cancer (Lebrun C et al. Eur. J. Neurol., 2007 Apr;14:470-2). 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. RCV003452933 SCV004188031 pathogenic Lynch syndrome 1 2023-07-26 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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