ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1170G>A (p.Ala390=) (rs755578413)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164461 SCV000215105 likely benign Hereditary cancer-predisposing syndrome 2014-07-04 criteria provided, single submitter clinical testing
Color RCV000164461 SCV000686101 likely benign Hereditary cancer-predisposing syndrome 2017-02-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781743 SCV000920032 uncertain significance not specified 2018-02-14 criteria provided, single submitter clinical testing Variant summary: PMS2 c.1170G>A alters a non-conserved nucleotide resulting in a synonymous change. 4/5 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 4.5e-05 in 242638 control chromosomes in gnomAD. This frequency is not significantly higher than expected for a pathogenic variant in PMS2 causing Lynch Syndrome (4.5e-05 vs 1.10E-04), allowing no conclusion about variant significance. However, the frequency in gnomAD may not be accurate due to the sequencing technology used being unable to distinguish between PMS2 and its pseudogenes. To our knowledge, no occurrence of c.1170G>A in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000232574 SCV000285049 likely benign Hereditary nonpolyposis colon cancer 2017-12-07 criteria provided, single submitter clinical testing

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