rs727504233
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM4PP3PP5_Moderate
The NM_005228.5(EGFR):c.2236_2250delGAATTAAGAGAAGCA(p.Glu746_Ala750del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
EGFR
NM_005228.5 conservative_inframe_deletion
NM_005228.5 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.89
Genes affected
EGFR (HGNC:3236): (epidermal growth factor receptor) The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor, thus inducing receptor dimerization and tyrosine autophosphorylation leading to cell proliferation. Mutations in this gene are associated with lung cancer. EGFR is a component of the cytokine storm which contributes to a severe form of Coronavirus Disease 2019 (COVID-19) resulting from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_005228.5.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 7-55174772-GGAATTAAGAGAAGCA-G is Pathogenic according to our data. Variant chr7-55174772-GGAATTAAGAGAAGCA-G is described in ClinVar as [Pathogenic]. Clinvar id is 177620.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| EGFR | ENST00000275493.7 | c.2236_2250delGAATTAAGAGAAGCA | p.Glu746_Ala750del | conservative_inframe_deletion | Exon 19 of 28 | 1 | NM_005228.5 | ENSP00000275493.2 | ||
| EGFR | ENST00000455089.5 | c.2101_2115delGAATTAAGAGAAGCA | p.Glu701_Ala705del | conservative_inframe_deletion | Exon 18 of 26 | 1 | ENSP00000415559.1 | |||
| EGFR | ENST00000450046.2 | c.2077_2091delGAATTAAGAGAAGCA | p.Glu693_Ala697del | conservative_inframe_deletion | Exon 19 of 28 | 4 | ENSP00000413354.2 | |||
| EGFR | ENST00000700145.1 | c.583_597delGAATTAAGAGAAGCA | p.Glu195_Ala199del | conservative_inframe_deletion | Exon 6 of 9 | ENSP00000514824.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lung adenocarcinoma Pathogenic:1
-
Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
not provided Pathogenic:1
Jan 01, 2021
CeGaT Center for Human Genetics Tuebingen
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Tyrosine kinase inhibitor response Other:1
Jan 16, 2007
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: drug response
Review Status: no assertion criteria provided
Collection Method: clinical testing
- Responsive
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at