ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.450+15G>T (rs10424545)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039483 SCV000063170 benign not specified 2012-06-13 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000039483 SCV000314688 benign not specified criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000039483 SCV001363495 benign not specified 2019-08-19 criteria provided, single submitter clinical testing Variant summary: MAP2K2 c.450+15G>T 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. Several computational tools predict a significant impact on normal splicing: Three predict that the variant creates a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.012 in 249874 control chromosomes, predominantly at a frequency of 0.16 within the African or African-American subpopulation in the gnomAD database, including 209 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 64000-folds over 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 found primarily in populations of African or African-American origin. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.

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