ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.853G>A (p.Asp285Asn) (rs150369301)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000680294 SCV000207964 likely benign not provided 2017-11-28 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000158029 SCV000604142 uncertain significance not specified 2017-03-10 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000158029 SCV000709725 uncertain significance not specified 2018-03-06 criteria provided, single submitter clinical testing Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: GnomAd 19:4099304 C / T: Total 4/230480; not well conserved Platypus, Naked_mole rat, and Zebra_mbuna(fish) have threonine; Not in Pubmed, Google search or HGMD; VUS by GeneDx in ClinVar; benign by polyphen
Invitae RCV001480813 SCV001685139 likely benign Rasopathy 2020-06-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000158029 SCV001983670 likely benign not specified 2021-09-26 criteria provided, single submitter clinical testing Variant summary: MAP2K2 c.853G>A (p.Asp285Asn) results in a conservative amino acid change located in the Protein kinase domain (IPR000179) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.1e-05 in 231844 control chromosomes. The observed variant frequency is approximately 121 fold of the estimated maximal expected allele frequency for a pathogenic variant in MAP2K2 causing Cardiofaciocutaneous Syndrome phenotype (7.5e-07), strongly suggesting that the variant is benign. c.853G>A has been reported in the literature as a VUS in settings of multigene panel testing for individuals affected with cardiomyopathy (example, Aljeaid_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiofaciocutaneous Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign, n=2; VUS, n=2). Based on the evidence outlined above, the variant was classified as likely benign.
Service de Génétique Moléculaire,Hôpital Robert Debré RCV001261064 SCV001438466 uncertain significance Noonan syndrome no assertion criteria provided clinical testing

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