15-66435116-A-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Moderate
The NM_002755.4(MAP2K1):c.170A>T(p.Lys57Met) 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K57Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_002755.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K1 | NM_002755.4 | c.170A>T | p.Lys57Met | missense_variant | 2/11 | ENST00000307102.10 | |
MAP2K1 | NM_001411065.1 | c.104A>T | p.Lys35Met | missense_variant | 2/10 | ||
MAP2K1 | XM_011521783.4 | c.104A>T | p.Lys35Met | missense_variant | 2/11 | ||
MAP2K1 | XM_017022411.3 | c.170A>T | p.Lys57Met | missense_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K1 | ENST00000307102.10 | c.170A>T | p.Lys57Met | missense_variant | 2/11 | 1 | NM_002755.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2022 | Published functional studies demonstrate the K57M variant increases ERK phosphorylation activation and cell cycle progression (Chen et al., 2020); Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31972311, 25370473, 22753777, 19156172, 26399658, 22177953, 29493581) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.