EGFR c.2127_2129del, p.Glu709_Thr710delinsAsp
NM_005228.5:c.2127_2129del
COSM51525
Population Frequency
0.0 in 100,000
Rare
ClinVar Classification
Pathogenic
1 publications
REVEL Score
N/A
Not Available
COSMIC Recurrence
17 occurrences
No Criteria Applied
Classification Evidence
Detailed Information
Genetic Information
Gene & Transcript Details
Gene
EGFR
Transcript
NM_005228.5
MANE Select
Total Exons
28
Strand
Forward (+)
Reference Sequence
NC_000007.13
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_005228.3 | Alternative | 28 exons | Forward |
| NM_005228.4 | Alternative | 28 exons | Forward |
Variant Details
HGVS Notation
NM_005228.5:c.2127_2129del
Protein Change
E709_T710delinsD
Location
Exon 18
(Exon 18 of 28)
5'
Exon Structure (28 total)
3'
Functional Consequence
Missense Variant
Related Variants
Alternate Identifiers
COSM51525
Variant interpretation based on transcript NM_005228.5
Clinical Evidence
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.0005%
0.001%
0.01%
0.05%
1%+
ACMG Criteria Applied
PM2
This variant is rare in the population (0.000000% MAF).
Classification
1 publications
Pathogenic
Based on 1 submitter review in ClinVar
Submitter Breakdown
Pathogenic
Likely Pathogenic
VUS
Likely Benign
Benign
Publications
1 publications
Show publication details
Clinical Statement
This variant has been reported in ClinVar as Pathogenic (1 clinical laboratories).
Functional Domain
Hotspot Status
Hotspot
PM1
Mutation Count
9
Reported mutations in this domain
0
50
100+
Domain Summary
This variant is located in a mutational hotspot or critical domain (9 mutations).
PM1 criterion applied: Located in a mutational hot spot and/or critical and well-established functional domain.
Related Variants in This Domain
Functional Studies
Summary
The EGFR E709_T710delinsD variant, located in the tyrosine kinase domain, has been functionally characterized as oncogenic. Experimental evidence indicates that this mutation is transforming and exhibits differential sensitivity to various EGFR inhibitors. It shows high sensitivity to second-generation inhibitors like afatinib, moderate sensitivity to first-generation inhibitors such as gefitinib, and resistance to third-generation inhibitors. Clinical data support these findings, with some patients showing stable or progressive disease on gefitinib or erlotinib, while others respond to afatinib. This variant has been observed in lung cancer cases, specifically non-small cell lung cancer. There is no mention of other pathogenic variants at the same position or codon.
Computational Evidence
Pathogenicity Predictions
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria
No VCEP interpretation available