ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.93-6C>T

gnomAD frequency: 0.00004  dbSNP: rs727504836
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156178 SCV000205894 uncertain significance not specified 2013-10-25 criteria provided, single submitter clinical testing The 93-6C>T variant in MEK2 has not been previously identified in individuals wi th Noonan spectrum disorders or in large population studies. This variant is loc ated in the 3' splice region and does not affect the coding sequence of the gene . Although we cannot rule out a deleterious impact on the regulation of splicing or translation of MEK2, to date no pathogenic variants have been found in this region of the transcript. In summary, additional studies are needed to fully ass ess the clinical significance of the 93-6C>T variant.
GeneDx RCV001711316 SCV000521903 likely benign not provided 2019-02-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000465734 SCV000561664 likely benign RASopathy 2024-12-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000156178 SCV001362372 benign not specified 2024-11-11 criteria provided, single submitter clinical testing Variant summary: MAP2K2 c.93-6C>T alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.5e-05 in 282392 control chromosomes. The observed variant frequency is approximately 14 fold of the estimated maximal expected allele frequency for a pathogenic variant in MAP2K2 causing Noonan Syndrome And Related Conditions phenotype (2.5e-06). To our knowledge, c.93-6C>T has not been reported in the literature in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 179389). Based on the evidence outlined above, the variant was classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813405 SCV002060585 likely benign Noonan syndrome and Noonan-related syndrome 2020-07-01 criteria provided, single submitter clinical testing

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