Submissions for variant NM_030662.4(MAP2K2):c.-27CCG[6]

dbSNP: rs397517411

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039468	SCV000063152	likely benign	not specified	2012-11-06	criteria provided, single submitter	clinical testing	-21_-16dupCCGCCG in the 5' UTR of MAP2K2: This variant has not been previously r eported in the literature or been identified in our laboratory. The 5' UTR plays a role in the regulation of gene expression and variants in this region have be en shown to alter protein translation (Mendell 2001, Scheper 2007). This type of variant has not been previously reported in individuals with Noonan spectrum di sorder.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039468	SCV004813275	benign	not specified	2024-06-14	criteria provided, single submitter	clinical testing	Variant summary: MAP2K2 c.-21_-16dupCCGCCG is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 1.1e-05 in 1404962 control chromosomes. The observed variant frequency is approximately 14 fold of the estimated maximal expected allele frequency for a pathogenic variant in MAP2K2 causing Cardiofaciocutaneous Syndrome phenotype (7.5e-07). To our knowledge, no occurrence of c.-21_-16dupCCGCCG in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 46225). Based on the evidence outlined above, the variant was classified as benign.