ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.255G>A (p.Leu85=) (rs200491279)

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Total submissions: 9
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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
Invitae RCV001082537 SCV000253299 likely benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000160903 SCV000537436 likely benign Hereditary cancer-predisposing syndrome 2015-04-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212839 SCV000697355 likely benign not specified 2019-01-02 criteria provided, single submitter clinical testing Variant summary: PMS2 c.255G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00018 in 269350 control chromosomes. The observed variant frequency is approximately 1.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in PMS2 causing Lynch Syndrome phenotype (0.00011), strongly suggesting that the variant is benign. c.255G>A has been reported in the literature in individuals affected with breast cancer (Caminsky_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Counsyl RCV000662801 SCV000785621 likely benign Hereditary nonpolyposis colorectal cancer 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 Hereditary nonpolyposis colorectal cancer type 4 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000587054 SCV001155037 likely benign not provided 2017-06-01 criteria provided, single submitter clinical testing

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