Submissions for variant NM_030662.4(MAP2K2):c.498C>T (p.Pro166=)

gnomAD frequency: 0.00076  dbSNP: rs139404261

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000458075	SCV000616580	benign	RASopathy	2017-05-09	reviewed by expert panel	curation	The filtering allele frequency of the c.498C>T (p.Pro166=) variant in the MAP2K2 gene is 0.081% (37/33932) of European 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, Mass General Brigham Personalized Medicine	RCV000039485	SCV000063173	likely benign	not specified	2012-11-13	criteria provided, single submitter	clinical testing	Pro166Pro in exon 4 of MAP2K2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.13% (11/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; dbSNP rs139404261).
PreventionGenetics, part of Exact Sciences	RCV000039485	SCV000314690	likely benign	not specified		criteria provided, single submitter	clinical testing
Invitae	RCV000458075	SCV000561660	benign	RASopathy	2024-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726603	SCV000701758	uncertain significance	not provided	2016-10-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000726603	SCV001939678	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813313	SCV002060577	benign	Noonan syndrome and Noonan-related syndrome	2019-04-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000726603	SCV002063706	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	MAP2K2: BP4, BP7
Ambry Genetics	RCV002336106	SCV002643524	benign	Cardiovascular phenotype	2020-11-30	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Clinical Genetics, Academic Medical Center	RCV000039485	SCV001920797	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000726603	SCV001967048	likely benign	not provided		no assertion criteria provided	clinical testing