ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.255G>A (p.Leu85=)

gnomAD frequency: 0.00022  dbSNP: rs200491279
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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212839 SCV000211598 benign not specified 2014-08-06 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000160903 SCV000212742 likely benign Hereditary cancer-predisposing syndrome 2014-07-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001082537 SCV000253299 likely benign Hereditary nonpolyposis colorectal neoplasms 2021-12-18 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000160903 SCV000537436 likely benign Hereditary cancer-predisposing syndrome 2015-04-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212839 SCV000697355 benign not specified 2021-03-01 criteria provided, single submitter clinical testing
Counsyl RCV000662801 SCV000785621 likely benign Colorectal cancer, hereditary nonpolyposis, type 4 2017-10-16 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000587054 SCV000806211 likely benign not provided 2017-04-03 criteria provided, single submitter clinical testing
Mendelics RCV000662801 SCV001137329 likely benign Colorectal cancer, hereditary nonpolyposis, type 4 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000587054 SCV001155037 likely benign not provided 2022-08-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587054 SCV001470057 likely benign not provided 2019-10-07 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001798557 SCV002042804 likely benign Breast and/or ovarian cancer 2021-03-20 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000212839 SCV002072407 likely benign not specified 2021-10-08 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000160903 SCV002530317 likely benign Hereditary cancer-predisposing syndrome 2021-03-19 criteria provided, single submitter curation
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355358 SCV001550228 likely benign Endometrial carcinoma no assertion criteria provided clinical testing The PMS2 p.Leu85= variant was not identified in the literature nor was it identified in the Genesight-COGR, Cosmic, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, and Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs200491279) “With Likely benign allele”, ClinVar (as benign by GeneDx, and likely benign by Ambry Genetics, Invitae and Color Genomics Inc.), Clinvitae (3x), and in control databases in 49 of 269350 chromosomes at a frequency of 0.0002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017) being identified in the following populations: Other in 1 of 6368 chromosomes (frequency: 0.0002), Latino in 2 of 34332 chromosomes (frequency: 0.00006), European Non-Finnish in 45 of 123320 chromosomes (frequency: 0.0004) and in South Asian in 1 of 30744 chromosomes (frequency: 0.00003). The p.Leu85 variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000587054 SCV001929597 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000587054 SCV001957120 likely benign not provided no assertion criteria provided clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000160903 SCV002050296 likely benign Hereditary cancer-predisposing syndrome 2021-12-21 no assertion criteria provided clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000212839 SCV002550757 likely benign not specified 2021-09-03 no assertion criteria provided clinical testing

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