Submissions for variant NM_030662.4(MAP2K2):c.420C>T (p.Asp140=)

gnomAD frequency: 0.00016  dbSNP: rs369925884

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000521680	SCV000616582	benign	RASopathy	2017-05-09	reviewed by expert panel	curation	The filtering allele frequency of the c.420C>T (p.Asp140=) variant in the MAP2K2 gene is 0.271% (32/8604) of East Asian 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)
PreventionGenetics, part of Exact Sciences	RCV000039481	SCV000314687	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000039481	SCV000513521	benign	not specified	2015-06-08	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	RCV000587230	SCV000699637	benign	not provided	2016-11-14	criteria provided, single submitter	clinical testing	Variant summary: The MAP2K2 c.420C>T (p.Asp140Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 45/121454 control chromosomes (1 homozygote) at a frequency of 0.0003705, which is approximately 148 times the estimated maximal expected allele frequency of a pathogenic MAP2K2 variant (0.0000025), suggesting this variant is likely a benign polymorphism. The variant has been reported in patients/families with metachondromatosis, autism and carcinoma of large intestine, without strong evidence for pathogenicity (COSMIC, Bowen_2011, Kelleher_2012). In addition, multiple clinical diagnostic laboratories have classified this variant as benign. Taken together, this variant is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000521680	SCV000776924	benign	RASopathy	2024-01-25	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813365	SCV002060575	benign	Noonan syndrome and Noonan-related syndrome	2021-01-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002326746	SCV002627335	likely benign	Cardiovascular phenotype	2022-03-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039481	SCV000063168	benign	not specified	2009-06-26	no assertion criteria provided	clinical testing