ClinVar Miner

Submissions for variant NM_030662.3(MAP2K2):c.395G>A (p.Gly132Asp) (rs387906800)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Miraca Genetics Laboratories, RCV000149835 SCV000196679 pathogenic Rasopathy no assertion criteria provided clinical testing Variant classified using ACMG guidelines
GeneDx RCV000413893 SCV000490606 likely pathogenic not provided 2015-12-02 criteria provided, single submitter clinical testing The G132D likely pathogenic variant has been reported previously in association with cardiofaciocutaneous (CFC) syndrome (Linden et al., 2011). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. G132D is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the protein kinase domain that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same residue (G132V) and in nearby residues (P128Q/R, W134H/C) have been reported in the Human Gene Mutation Database in association with CFC syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Additionally, MAP2K2 has a low rate of benign missense variation and missense variants are a common mechanism of disease in this gene. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
OMIM RCV000023088 SCV000044379 pathogenic Cardiofaciocutaneous syndrome 4 2011-04-01 no assertion criteria provided literature only

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