ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2559C>T (p.Ile853=)

dbSNP: rs371673459
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163176 SCV000213697 likely benign Hereditary cancer-predisposing syndrome 2014-12-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000228797 SCV000285125 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589686 SCV000697354 likely benign not specified 2019-08-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284328 SCV001470056 likely benign not provided 2022-09-13 criteria provided, single submitter clinical testing
GeneDx RCV001284328 SCV001858514 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000589686 SCV002550677 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003492671 SCV004239597 likely benign Breast and/or ovarian cancer 2023-03-29 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000163176 SCV004358949 likely benign Hereditary cancer-predisposing syndrome 2022-05-24 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355440 SCV001550326 likely benign Carcinoma of colon no assertion criteria provided clinical testing The PMS2 p.Ile853= variant was not identified in the literature. The variant was identified in dbSNP (rs371673459) as “with uncertain significance allele” and ClinVar (classified as likely benign by Invitae and Ambry Genetics and uncertain significance by Integrated Genetics). The variant was identified in control databases in 2 of 203,794 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 2 of 89,196 chromosomes (freq: 0.00002), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, Finnish, Other and South Asian populations. The p.Ile853= 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. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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.

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