Submissions for variant NM_030662.4(MAP2K2):c.981C>T (p.Asn327=)

gnomAD frequency: 0.00011  dbSNP: rs143275018

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039499	SCV000063188	benign	not specified	2011-06-09	criteria provided, single submitter	clinical testing	Asn327Asn in exon 8 of MEK2: This variant is not expected to have clinical or pa thological significance because it does not alter an amino acid residue and is n ot located near a splice junction. This variant has been identified in 2/732 (0. 2%) of Caucasian probands tested by our laboratory; one of those individuals als o had a pathogenic RAF1 variant.
Invitae	RCV001080291	SCV000561661	likely benign	RASopathy	2024-01-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590665	SCV000699650	benign	not provided	2017-08-10	criteria provided, single submitter	clinical testing	Variant summary: The MAP2K2 c.981C>T (p.Asn327Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 14/119582 control chromosomes at a frequency of 0.0001171, which is approximately 47 times the estimated maximal expected allele frequency of a pathogenic MAP2K2 variant (0.0000025), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV000590665	SCV001939681	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002371816	SCV002689238	likely benign	Cardiovascular phenotype	2022-07-06	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.
CeGaT Center for Human Genetics Tuebingen	RCV000590665	SCV004141446	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	MAP2K2: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003934877	SCV004764762	likely benign	MAP2K2-related disorder	2019-03-18	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).