ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2445T>A (p.Tyr815Ter)

dbSNP: rs1667403360
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001388596 SCV001589650 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-06-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr815*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has not been reported in the literature in individuals with MSH2-related conditions. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV002456607 SCV002736761 pathogenic Hereditary cancer-predisposing syndrome 2018-05-30 criteria provided, single submitter clinical testing The p.Y815* pathogenic mutation (also known as c.2445T>A), located in coding exon 14 of the MSH2 gene, results from a T to A substitution at nucleotide position 2445. This changes the amino acid from a tyrosine to a stop codon within coding exon 14. 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. RCV003451684 SCV004188941 pathogenic Lynch syndrome 1 2023-08-08 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.
deCODE genetics, Amgen RCV003451684 SCV004022227 pathogenic Lynch syndrome 1 2023-07-21 no assertion criteria provided research The variant NM_000251.3:c.2445T>A (chr2:47478506) in MSH2 was detected in 5 heterozygotes out of 58K WGS Icelanders (MAF= 0,004%). Following imputation in a set of 166K Icelanders (12 imputed heterozygotes) we observed an association with colorectal cancer using 4991 cases and 314812 controls (OR= 14.51, P= 1.01e-04). This variant has been reported in ClinVar previously as pathogenic. Based on ACMG criteria (PVS1, PS4) this variant classifies as pathogenic.

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