ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1609G>A (p.Glu537Lys) (rs115052399)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000127463 SCV000171030 benign not specified 2014-01-15 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 RCV000165452 SCV000216182 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Invitae RCV001082898 SCV000262253 benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000204752 SCV000469726 likely benign Hereditary nonpolyposis colorectal cancer type 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Color RCV000165452 SCV000686144 benign Hereditary cancer-predisposing syndrome 2015-01-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590728 SCV000697303 likely benign not provided 2016-06-15 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.1609G>A (p.Glu537Lys) variant causes a missense change involving a non-conserved nucleotide with 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 124/120170 (1 homozygote, 1/968), predominantly in the African cohort, 122/10000 (1 homozygote, 1/81), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic PMS2 variant of 1/8802 (0.0001136). Even though this observed frequency is higher than expected for the pathogenic variant, we must use controls data with caution due to presence of a pseudogene. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; however, reputable clinical diagnostic laboratories cite the variant as "benign." Therefore, taking all available lines of evidence, the variant of interest has been classified as Likely Benign.
PreventionGenetics,PreventionGenetics RCV000127463 SCV000806182 benign not specified 2017-04-25 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000127463 SCV000859816 benign not specified 2018-03-09 criteria provided, single submitter clinical testing

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