rs397517116
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4PP5
The NM_005228.5(EGFR):c.2317_2322dup(p.His773_Val774dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P772P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Consequence
EGFR
NM_005228.5 inframe_insertion
NM_005228.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.13
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.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 12 uncertain in NM_005228.5
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_005228.5.
PP5
?
Variant 7-55181325-C-CCACGTG is Pathogenic according to our data. Variant chr7-55181325-C-CCACGTG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 45262.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.2317_2322dup | p.His773_Val774dup | inframe_insertion | 20/28 | ENST00000275493.7 | |
EGFR-AS1 | NR_047551.1 | n.1245_1246insCACGTG | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.2317_2322dup | p.His773_Val774dup | inframe_insertion | 20/28 | 1 | NM_005228.5 | P1 | |
EGFR-AS1 | ENST00000442411.2 | n.1273_1274insCACGTG | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Non-small cell lung carcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 01, 2008 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at