ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2502_2508del (p.Asn835fs) (rs63751447)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076489 SCV000107518 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000163822 SCV000214407 pathogenic Hereditary cancer-predisposing syndrome 2018-05-21 criteria provided, single submitter clinical testing The c.2502_2508delTAATTTC pathogenic mutation, located in coding exon 15 of the MSH2 gene, results from a deletion of 7 nucleotides at nucleotide positions 2502 to 2508, causing a translational frameshift with a predicted alternate stop codon (p.N835Lfs*4). This mutation has been reported in numerous affected individuals whose families met Amsterdam or Bethesda criteria and whose tumors showed high microsatellite instability and/or absent MSH2 staining on IHC (Scott RJ et al. Am. J. Hum. Genet. 2001 Jan;68:118-127; Coleman MG et al. Br. J. Cancer 2001 Nov;85:1486-91; Ward R et al. J. Cancer Res. Clin. Oncol. 2002 Aug;128:403-11). 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.
GeneDx RCV000202117 SCV000568055 pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing This deletion of seven nucleotides in MSH2 is denoted c.2502_2508delTAATTTC at the cDNA level and p.Asn835LeufsX4 (N835LfsX4) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TTGC[delTAATTTC]CCTA. The deletion causes a frameshift, which changes an Asparagine to a Leucine at codon 835, and creates a premature stop codon at position 4 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH2 c.2502_2508delTAATTTC has been observed in multiple individuals with Lynch syndrome associated cancers (Scott 2001, Sjursen 2016). Based on currently available information, we consider MSH2 c.2502_2508delTAATTTC to be pathogenic.
Invitae RCV001051236 SCV001215380 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-07-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn835Leufs*4) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 11112663, 12200596). ClinVar contains an entry for this variant (Variation ID: 90987). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000202117 SCV000257179 likely pathogenic not provided no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.