rs397517412
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_030662.4(MAP2K2):c.287_288delinsGT(p.Leu96Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 33)
Consequence
MAP2K2
NM_030662.4 missense
NM_030662.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.20
Genes affected
MAP2K2 (HGNC:6842): (mitogen-activated protein kinase kinase 2) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAP2K2 | NM_030662.4 | c.287_288delinsGT | p.Leu96Arg | missense_variant | 2/11 | ENST00000262948.10 | NP_109587.1 | |
MAP2K2 | XM_006722799.3 | c.287_288delinsGT | p.Leu96Arg | missense_variant | 2/9 | XP_006722862.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAP2K2 | ENST00000262948.10 | c.287_288delinsGT | p.Leu96Arg | missense_variant | 2/11 | 1 | NM_030662.4 | ENSP00000262948 | P1 | |
MAP2K2 | ENST00000394867.9 | n.726_727delinsGT | non_coding_transcript_exon_variant | 1/10 | 5 | |||||
MAP2K2 | ENST00000599345.1 | n.484_485delinsGT | non_coding_transcript_exon_variant | 2/7 | 5 | |||||
MAP2K2 | ENST00000687128.1 | n.726_727delinsGT | non_coding_transcript_exon_variant | 1/7 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 16, 2012 | The Leu96Arg variant in MEK2 has not been reported in the literature nor previou sly identified in our laboratory. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Leu9 6Arg variant may impact the protein, though this information is not predictive e nough to determine pathogenicity. In summary, additional information is needed to fully assess the clinical significance of the Leu96Arg variant. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | MAP2K2: PM2, PS2:Moderate - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at