ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.1194C>T (p.Thr398=) (rs144850779)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000205301 SCV000616561 benign Rasopathy 2017-05-09 reviewed by expert panel curation The filtering allele frequency of the c.1194C>T (p.Thr398=) variant in the MAP2K2 gene is 0.159% (19/7836) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039472 SCV000063157 likely benign not specified 2010-12-21 criteria provided, single submitter clinical testing
Invitae RCV000205301 SCV000260142 likely benign Rasopathy 2020-10-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590246 SCV000699630 benign not provided 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The c.1194C>T (p.Thr398=) in MAP2K2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.00097 (19/19528chrs tested) exclusively in individuals of European origin (0.0024; 19/7836). However ExAC includes a warning note, this variant is only covered in 9764 individuals (adjusted allele number = 19528). This means that the site is covered in fewer than 80% of the individuals in ExAC, which may indicate a low-quality site. Regardless, this frequency exceeds the maximal expected frequency of a pathogenic allele (0.0000025) in this gene. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but was cited as Likely Benign by reputable databases/clinical laboratory. Taking together, based on the prevalence in the general population, the synonymous nature of the variant and the lack of predicted effect on splicing, the variant was classified as Benign.

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