Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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, |
RCV000039472 | SCV000063157 | likely benign | not specified | 2010-12-21 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000205301 | SCV000260142 | likely benign | RASopathy | 2024-01-06 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
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. |
Gene |
RCV000590246 | SCV001939683 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002336107 | SCV002644807 | likely benign | Cardiovascular phenotype | 2020-01-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |