rs397517096
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_005228.5(EGFR):c.2239_2240delinsCC(p.Leu747Pro) variant causes a missense 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 Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L747S) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 33)
Consequence
EGFR
NM_005228.5 missense
NM_005228.5 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.93
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 Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a hotspot region, there are 7 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 14 uncertain in NM_005228.5
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.2239_2240delinsCC | p.Leu747Pro | missense_variant | 19/28 | ENST00000275493.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.2239_2240delinsCC | p.Leu747Pro | missense_variant | 19/28 | 1 | NM_005228.5 | P1 | |
EGFR | ENST00000455089.5 | c.2104_2105delinsCC | p.Leu702Pro | missense_variant | 18/26 | 1 | |||
EGFR | ENST00000450046.2 | c.2080_2081delinsCC | p.Leu694Pro | missense_variant | 19/28 | 4 | |||
EGFR | ENST00000700145.1 | c.588_589delinsCC | p.Leu197Pro | missense_variant | 6/9 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 27, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at