ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1242C>T (p.Asp414=) (rs142839559)

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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 RCV000166893 SCV000217710 likely benign Hereditary cancer-predisposing syndrome 2014-12-08 criteria provided, single submitter clinical testing
Color RCV000166893 SCV000686110 likely benign Hereditary cancer-predisposing syndrome 2016-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589485 SCV000697288 likely benign not provided 2017-07-21 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.1242C>T (p.Asp414Asp) variant involves the alteration of a non-conserved nucleotide causes a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 37/277098 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.001124 (27/24012). This frequency is about 10 times the estimated maximal expected allele frequency of a pathogenic PMS2 variant (0.0001136), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. However, this observation needs to be cautiously considered due to the possibility of the PMS2 pseudogene being captured. An internal LCA sample has reported the variant to co-occur with a pathogenic PMS2 variant, c.2186_2187delTC. Since its previous classification as a VUS-possibly benign, one additional clinical diagnostic laboratory in ClinVar database has classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, the classification of this variant has been updated to likely benign.
Invitae RCV000229081 SCV000285056 benign Hereditary nonpolyposis colon cancer 2017-11-01 criteria provided, single submitter clinical testing

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