Genetic Information

Gene & Transcript Details

Gene
PTPN11
Transcript
NM_001330437.1 MANE Select
Total Exons
—
Reference Sequence
NC_000012.11
Alternative Transcripts
IDStatusDetails
NM_001330437.2 Alternative 6085 nt | 166–1959
NM_001330437.1 Alternative 6151 nt | 215–2008

Variant Details

HGVS Notation
NM_001330437.1:c.53A>G
Protein Change
N18S
Location
Exon 2 (Exon 2 of )
2
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.00954 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
Uncertain Significance (VUS)
3 publications
Clinical Statement

"This variant has been reported in ClinVar as Benign (5 clinical laboratories) and as Likely benign (2 clinical laboratories) and as Uncertain significance (1 clinical laboratories) and as Benign 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 PTPN11.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: PTPN11N18SPTPN11N18SSomaticNCBI Gene:5781|Show additional gene information Variant OverviewPTPN11, a protein tyrosine phosphatase, is altered in various solid and hematologic malignancies.The PTPN11 N18S mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. 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 -38 bp
- Donor Loss (DL) 0.0 84 bp
+ Acceptor Gain (AG) 0.0 158 bp
+ Donor Gain (DG) 0.0 294 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:
PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)