chr7-55181287-C-CTCCAGGAAGCCT

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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: -1.27
Variant links:
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]
EGFR-AS1 (HGNC:40207): (EGFR antisense RNA 1)

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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
EGFRNM_005228.5 linkuse as main transcriptc.2284-5_2290dup splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000275493.7
EGFR-AS1NR_047551.1 linkuse as main transcriptn.1283_1284insAGGCTTCCTGGA non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EGFRENST00000275493.7 linkuse as main transcriptc.2284-5_2290dup splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_005228.5 P1P00533-1
EGFR-AS1ENST00000442411.2 linkuse as main transcriptn.1311_1312insAGGCTTCCTGGA non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
31
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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJul 01, 2011This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs397517106; hg19: chr7-55248980; API