Submissions for variant NM_030662.3(MAP2K2):c.*8C>T

gnomAD frequency: 0.00014  dbSNP: rs377675706

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000523941	SCV000616546	likely benign	RASopathy	2017-05-09	reviewed by expert panel	curation	The c.*8C>T variant in MAP2K2 has been observed in at least 6 individuals who underwent testing for RASopathies (PS4 not met; GeneDx, LMM internal data; GTR ID's: 26957, 21766; SCV000063150.4, SCV000170190.9). This variant is a synonymous (silent) variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data, SCV000170190.9). In summary, this variant meets criteria to be classified as likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP7, BP5.
GeneDx	RCV000039466	SCV000170190	benign	not specified	2013-11-27	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039466	SCV000699626	benign	not specified	2018-08-13	criteria provided, single submitter	clinical testing	Variant summary: MAP2K2 c.*8C>T is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.00014 in 179598 control chromosomes. The observed variant frequency is approximately 55 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. c.*8C>T has been reported in the literature in individuals affected with autism. This report does not provide unequivocal conclusions about association of the variant with Noonan Syndrome and Related Conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinGen RASopathy Expert Panel has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign based on ACMG criteria BP5 and BP7 although the variant is not a synonymous variant type. Based on the evidence outlined above, the variant was classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813363	SCV002060566	likely benign	Noonan syndrome and Noonan-related syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039466	SCV000063150	uncertain significance	not specified	2009-02-10	no assertion criteria provided	clinical testing