ClinVar Miner

Submissions for variant NM_030662.3(MAP2K2):c.525C>T (p.Ile175=) (rs150833333)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000126671 SCV000616579 benign Rasopathy 2017-05-09 reviewed by expert panel curation The filtering allele frequency of the c.525C>T (p.Ile175=) variant in the MAP2K2 gene is 0.255% (11/2418) of Latino chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039487 SCV000063175 likely benign not specified 2009-05-07 criteria provided, single submitter clinical testing
GeneDx RCV000039487 SCV000170180 benign not specified 2012-01-12 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.
Invitae RCV000858768 SCV000260507 likely benign not provided 2019-02-04 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000039487 SCV000314692 likely benign not specified criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000039487 SCV000919605 benign not specified 2018-02-26 criteria provided, single submitter clinical testing Variant summary: MAP2K2 c.525C>T 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 0.00025 in 252824 control chromosomes. The observed variant frequency is approximately 98.092 fold of the estimated maximal expected allele frequency for a pathogenic variant in MAP2K2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.525C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Two 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 benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.