Submissions for variant NM_030662.4(MAP2K2):c.893C>T (p.Pro298Leu)

gnomAD frequency: 0.00034  dbSNP: rs200371894

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000227476	SCV000616566	benign	RASopathy	2017-05-09	reviewed by expert panel	curation	The filtering allele frequency of the c.893C>T (p.Pro298Leu) variant in the MAP2K2 gene is 0.953% (68/5776) 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)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154492	SCV000204162	benign	not specified	2015-10-22	criteria provided, single submitter	clinical testing	p.Pro298Leu in exon 7 of MAP2K2: This variant is not expected to have clinical s ignificance because it has been identified in 1.2% (68/5776) of East Asian chrom osomes, including 2 homozygotes, by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs200371894).
GeneDx	RCV000154492	SCV000207951	benign	not specified	2015-08-17	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	RCV000227476	SCV000290943	benign	RASopathy	2024-01-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586661	SCV000699648	benign	not provided	2016-10-24	criteria provided, single submitter	clinical testing	Variant summary: The MAP2K2 c.893C>T (p.Pro298Leu) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant was found in 79/73910 control chromosomes (2 homozygotes), predominantly observed in the East Asian subpopulation at a frequency of 0.0117729 (68/5776). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic MAP2K2 variant (0.0000025), srong evidence this is a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as 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.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852749	SCV000995467	benign	Hypertrophic cardiomyopathy	2018-03-22	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813317	SCV002060583	benign	Noonan syndrome and Noonan-related syndrome	2020-09-23	criteria provided, single submitter	clinical testing