ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2276-10A>G (rs573900018)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130505 SCV000185374 likely benign Hereditary cancer-predisposing syndrome 2014-11-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Counsyl RCV000662656 SCV000785343 likely benign Hereditary nonpolyposis colorectal cancer type 4 2017-07-07 criteria provided, single submitter clinical testing
GeneDx RCV000441367 SCV000520052 likely benign not specified 2017-07-21 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.
Integrated Genetics/Laboratory Corporation of America RCV000588652 SCV000697342 uncertain significance not provided 2017-02-02 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.2276-10A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 8/115980 control chromosomes at a frequency of 0.000069, which does not exceed the estimated maximal expected allele frequency of a pathogenic PMS2 variant (0.0001136). Since the variant is located in the highly homologous region and it is unknown if the presence in controls was verified by LRG-PCR, the occurrence data in general population needs to be taken with caution. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign without evidence to independently evaluate. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000203735 SCV000259806 likely benign Lynch syndrome 2015-08-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000441367 SCV000601841 likely benign not specified 2017-06-06 criteria provided, single submitter clinical testing

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