ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1840A>T (p.Lys614Ter) (rs63750490)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076831 SCV000108318 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research nonsense/frameshift
Ambry Genetics RCV000164595 SCV000215254 pathogenic Hereditary cancer-predisposing syndrome 2019-05-01 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000216236 SCV000279146 pathogenic not provided 2018-07-12 criteria provided, single submitter clinical testing This pathogenic variant is denoted PMS2 c.1840A>T at the cDNA level and p.Lys614Ter (K614X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with Lynch syndrome (Hampel 2008, Senter 2008, Yurgelun 2015) and is considered pathogenic.
Invitae RCV000540895 SCV000625560 pathogenic Hereditary nonpolyposis colon cancer 2019-11-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys614*) in the PMS2 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 reported in the heterozygous state in several individuals affected with colorectal cancer and/or endometrial cancer (PMID: 18602922, 22577899, 25856668), and in the homozygous state in several individuals affected with constitutional mismatch repair deficiency syndrome (PMID: 21376568, 22692065, 17993636). ClinVar contains an entry for this variant (Variation ID: 91318). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
Color RCV000164595 SCV000691046 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000076831 SCV000864157 pathogenic Lynch syndrome 2017-08-01 criteria provided, single submitter research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 66 year old female with a personal history of uterine cancer and family history of colorectal cancer. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000216236 SCV000889610 pathogenic not provided 2016-05-28 criteria provided, single submitter clinical testing

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