rs387906800
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_030662.4(MAP2K2):c.395G>T(p.Gly132Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G132D) has been classified as Likely pathogenic.
Frequency
Consequence
NM_030662.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K2 | NM_030662.4 | c.395G>T | p.Gly132Val | missense_variant | 3/11 | ENST00000262948.10 | |
MAP2K2 | XM_006722799.3 | c.395G>T | p.Gly132Val | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K2 | ENST00000262948.10 | c.395G>T | p.Gly132Val | missense_variant | 3/11 | 1 | NM_030662.4 | P1 | |
MAP2K2 | ENST00000394867.9 | n.834G>T | non_coding_transcript_exon_variant | 2/10 | 5 | ||||
MAP2K2 | ENST00000599345.1 | n.592G>T | non_coding_transcript_exon_variant | 3/7 | 5 | ||||
MAP2K2 | ENST00000687128.1 | n.834G>T | non_coding_transcript_exon_variant | 2/7 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
RASopathy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 03, 2021 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly132 amino acid residue in MAP2K2. Other variant(s) that disrupt this residue have been observed in individuals with MAP2K2-related conditions (PMID: 21178588), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MAP2K2 protein function. This variant has been observed in individual(s) with a diagnosis of, or clinical features of, cardiofaciocutaneous syndrome (PMID: 17366577, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 132 of the MAP2K2 protein (p.Gly132Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.