ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.383C>T (p.Ser128Leu) (rs116373169)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084082 SCV000166385 benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000128980 SCV000172866 likely benign Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);Subpopulation frequency in support of benign classification
GeneDx RCV000200993 SCV000211588 likely benign not specified 2017-12-28 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.
PreventionGenetics,PreventionGenetics RCV000200993 SCV000304735 likely benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000587673 SCV000333808 uncertain significance not provided 2015-09-11 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000200993 SCV000596471 benign not specified 2017-06-23 criteria provided, single submitter clinical testing
Color RCV000128980 SCV000686199 likely benign Hereditary cancer-predisposing syndrome 2015-10-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587673 SCV000697367 likely benign not provided 2016-02-01 criteria provided, single submitter clinical testing Variant summary: The c.383C>T variant affects a conserved nucleotide, resulting in amino acid change from Ser to Leu. 4/4 in-silico tools predict damaging outcome for this variant (SNPs&GO not captured due to low reliability index). 5/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions are not confirmed by experimental studies. This variant is found in 92/121400 control chromosomes at a frequency of 0.0007578, which is about 7 times of maximal expected frequency of a pathogenic allele (0.0001136), suggesting this variant is benign. Sequence alignment suggests alleles identified in ExAC controls are unlikely from PMS2 pseudogenes. In addition, multiple clinical laboratories/literature classified this variant as benign/likely benign/polymorphisms. Taken together, this variant was classified as likely benign.
Counsyl RCV000662720 SCV000785474 likely benign Hereditary nonpolyposis colorectal cancer type 4 2017-08-18 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000758689 SCV000887461 uncertain significance Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing PMS2 NM_000535.5:c.383C>T has a 14.1% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.16 to 1, generated from evidence of seeing this as a somatic mutation in a tumor with loss of heterozygosity at the PMS2 locus. See Shirts et al 2018, PMID 29887214.
Mendelics RCV000662720 SCV001137327 likely benign Hereditary nonpolyposis colorectal cancer type 4 2019-05-28 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000128980 SCV000788115 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing
Ding PR Lab,Sun Yat-sen University Cancer Center RCV001093681 SCV001250862 uncertain significance Lynch syndrome I no assertion criteria provided clinical testing

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