ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.705+11G>A

dbSNP: rs202086678
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Total submissions: 4
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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 RCV000219657 SCV000270399 likely benign not specified 2015-10-16 criteria provided, single submitter clinical testing c.705+11G>A in intron 6 of MAP2K2: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. I t has been identified in 0.2% (19/7954) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs202086678) .
PreventionGenetics, part of Exact Sciences RCV000219657 SCV000314701 likely benign not specified criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000219657 SCV001361145 benign not specified 2019-12-30 criteria provided, single submitter clinical testing Variant summary: MAP2K2 c.705+11G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational 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 0.00036 in 161918 control chromosomes, predominantly at a frequency of 0.002 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 800 fold of the estimated maximal expected allele frequency for a pathogenic variant in MAP2K2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.705+11G>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV002057113 SCV002409222 benign RASopathy 2024-01-29 criteria provided, single submitter clinical testing

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