Genetic Information

Gene & Transcript Details

Gene
MAP2K2
Transcript
NM_030662.4 MANE Select
Total Exons
—
Reference Sequence
NC_000019.9
Alternative Transcripts
IDStatusDetails
NM_030662.4 MANE Select 1727 nt | 248–1450
NM_030662.3 RefSeq Select 1759 nt | 255–1457
NM_030662.2 Alternative 1759 nt | 255–1457

Variant Details

HGVS Notation
NM_030662.4:c.383C>A
Protein Change
P128Q
Location
Exon 3 (Exon 3 of )
3
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Pathogenic
1 publications
Clinical Statement

"This variant has been reported in ClinVar as Pathogenic (1 clinical laboratories) and as Pathogenic by ClinGen RASopathy Variant Curation Expert Panel expert panel."

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene MAP2K2.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: MAP2K2P128QMAP2K2P128QSomaticNCBI Gene:5605|Show additional gene information Variant OverviewMAP2K2, an intracellular kinase, is altered by mutation in various cancer types.The MAP2K2 P128Q mutation has not specifically been reviewed by the OncoKB team. However, MAP2K2 P128L is likely oncogenic, and therefore MAP2K2 P128Q is considered likely oncogenic.Hide mutation effect description The MAP2K2 P128Q mutation has not specifically been reviewed by the OncoKB team. However, the mutation effect description for MAP2K2 P128L, an alternate allele of MAP2K2 P128Q, is: The MEK2 P128L mutation is located in the kinase domain of the protein. Expression of this mutation in an embryonic kidney cell line demonstrated that it is likely activating as measured by increased protein activation compared to wildtype (PMID: 32641410). JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 105 bp
- Donor Loss (DL) 0.01 242 bp
+ Acceptor Gain (AG) 0.0 -161 bp
+ Donor Gain (DG) 0.0 379 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PP5

PP5 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)