rs397517106
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_005228.5(EGFR):c.2284-5_2290dup variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Consequence
EGFR
NM_005228.5 splice_region, splice_polypyrimidine_tract, intron
NM_005228.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.27
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-55181287-C-CTCCAGGAAGCCT is Pathogenic according to our data. Variant chr7-55181287-C-CTCCAGGAAGCCT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 45248.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.2284-5_2290dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000275493.7 | |||
EGFR-AS1 | NR_047551.1 | n.1283_1284insAGGCTTCCTGGA | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.2284-5_2290dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005228.5 | P1 | |||
EGFR-AS1 | ENST00000442411.2 | n.1311_1312insAGGCTTCCTGGA | 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: criteria provided, single submitter
LINK: link
Submissions by phenotype
Non-small cell lung carcinoma Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 01, 2011 | This variant is a duplication at the 5' intron/exon boundary of exon 20 which results in the insertion of four amino acids. This variant has previously been reported in the literature in one lung carcinoma (Chen 2008, COSMIC). Insertions in EGFR exon 20 such as this have been associated with resistance to EGFR tyrosine kinase inhibitors; however, the likelihood of responsiveness of this individual cannot be determined conclusively. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at