chr19-4110564-C-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PM5PP3_ModeratePP5_Very_Strong
The NM_030662.4(MAP2K2):c.395G>A(p.Gly132Asp) 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. G132V) 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 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K2 | NM_030662.4 | c.395G>A | p.Gly132Asp | missense_variant | 3/11 | ENST00000262948.10 | |
MAP2K2 | XM_006722799.3 | c.395G>A | p.Gly132Asp | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K2 | ENST00000262948.10 | c.395G>A | p.Gly132Asp | missense_variant | 3/11 | 1 | NM_030662.4 | P1 | |
MAP2K2 | ENST00000394867.9 | n.834G>A | non_coding_transcript_exon_variant | 2/10 | 5 | ||||
MAP2K2 | ENST00000599345.1 | n.592G>A | non_coding_transcript_exon_variant | 3/7 | 5 | ||||
MAP2K2 | ENST00000687128.1 | n.834G>A | non_coding_transcript_exon_variant | 2/7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cardiofaciocutaneous syndrome 4 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2011 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Apr 23, 2020 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24803665, 31040167, 25370473, 22753777, 19156172, 26399658, 22177953, 29493581, 34184824, 21178588, 36964972) - |
RASopathy Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Baylor Genetics | - | Variant classified using ACMG guidelines - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at