ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.844C>T (p.Pro282Ser) (rs142307980)

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 RCV000522371 SCV000616548 benign Rasopathy 2017-05-09 reviewed by expert panel curation The filtering allele frequency of the c.844C>T (p.Pro282Ser) variant in the MAP2K2 gene is 0.029% for African chromosomes by the Exome Aggregation Consortium (19/6048 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1).This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data; GTR ID's 26957; SCV000207963.8). In summary, this variant meets criteria to be classified as benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BA1, BP5.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039495 SCV000063184 likely benign not specified 2015-09-29 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000680293 SCV000207963 benign not provided 2016-06-03 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 RCV000522371 SCV001003111 likely benign Rasopathy 2020-11-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000039495 SCV001363494 benign not specified 2019-07-08 criteria provided, single submitter clinical testing Variant summary: MAP2K2 c.844C>T (p.Pro282Ser) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00025 in 263182 control chromosomes including one homozygote, predominantly at a frequency of 0.0018 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 720 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 a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.844C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions including one expert panel (ClinGen RASopathy Variant Curation) (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Service de Génétique Moléculaire,Hôpital Robert Debré RCV000824950 SCV000965985 uncertain significance Noonan syndrome no assertion criteria provided clinical testing

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.