chr15-66435117-G-T
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PS1PM1PM2PM5PP2PP3_ModeratePP5_Moderate
The NM_002755.4(MAP2K1):c.171G>T(p.Lys57Asn) variant causes a missense change involving the alteration of a non-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 nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. 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 15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K1 | NM_002755.4 | c.171G>T | p.Lys57Asn | missense_variant | 2/11 | ENST00000307102.10 | |
MAP2K1 | NM_001411065.1 | c.105G>T | p.Lys35Asn | missense_variant | 2/10 | ||
MAP2K1 | XM_011521783.4 | c.105G>T | p.Lys35Asn | missense_variant | 2/11 | ||
MAP2K1 | XM_017022411.3 | c.171G>T | p.Lys57Asn | missense_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K1 | ENST00000307102.10 | c.171G>T | p.Lys57Asn | 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
Melorheostosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 23, 2020 | - - |
Lung adenocarcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Jul 14, 2015 | - - |
Melanoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Dec 26, 2014 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital | Apr 26, 2021 | This variant has been previously reported in several unrelated individuals with arteriovenous malformations, and in vitro functional studies have demonstrated that the p.Lys57Asn substitution results in activation of downstream signaling (PMID: 28190454, PMID: 29461977). This variant has not been observed in large population studies (Genome Aggregation Database v2.1.1). - |
Non-small cell lung carcinoma Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Oct 02, 2014 | - - |
Cardio-facio-cutaneous syndrome Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at