Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156178 | SCV000205894 | uncertain significance | not specified | 2013-10-25 | criteria provided, single submitter | clinical testing | The 93-6C>T variant in MEK2 has not been previously identified in individuals wi th Noonan spectrum disorders or in large population studies. This variant is loc ated in the 3' splice region and does not affect the coding sequence of the gene . Although we cannot rule out a deleterious impact on the regulation of splicing or translation of MEK2, to date no pathogenic variants have been found in this region of the transcript. In summary, additional studies are needed to fully ass ess the clinical significance of the 93-6C>T variant. |
| Gene |
RCV001711316 | SCV000521903 | likely benign | not provided | 2019-02-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000465734 | SCV000561664 | likely benign | RASopathy | 2024-02-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000156178 | SCV001362372 | likely benign | not specified | 2019-12-30 | criteria provided, single submitter | clinical testing | Variant summary: MAP2K2 c.93-6C>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. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.6e-05 in 250996 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, c.93-6C>T has not been reported in the literature in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Genome Diagnostics Laboratory, |
RCV001813405 | SCV002060585 | likely benign | Noonan syndrome and Noonan-related syndrome | 2020-07-01 | criteria provided, single submitter | clinical testing |