rs727504257

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP3

The NM_005228.5(EGFR):​c.2238_2251delATTAAGAGAAGCAAinsGC​(p.Leu747_Thr751delinsPro) variant causes a disruptive inframe deletion, synonymous 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 drug response (★).

Frequency

Genomes: not found (cov: 33)

Consequence

EGFR
NM_005228.5 disruptive_inframe_deletion, synonymous

Scores

Not classified

Clinical Significance

drug response criteria provided, single submitter O:1

Conservation

PhyloP100: 9.89
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EGFRNM_005228.5 linkc.2238_2251delATTAAGAGAAGCAAinsGC p.Leu747_Thr751delinsPro disruptive_inframe_deletion, synonymous_variant 19/28 ENST00000275493.7 NP_005219.2 P00533-1Q504U8F2YGG7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EGFRENST00000275493.7 linkc.2238_2251delATTAAGAGAAGCAAinsGC p.Leu747_Thr751delinsPro disruptive_inframe_deletion, synonymous_variant 19/281 NM_005228.5 ENSP00000275493.2 P00533-1
EGFRENST00000455089.5 linkc.2103_2116delATTAAGAGAAGCAAinsGC p.Leu702_Thr706delinsPro disruptive_inframe_deletion, synonymous_variant 18/261 ENSP00000415559.1 Q504U8
EGFRENST00000450046.2 linkc.2079_2092delATTAAGAGAAGCAAinsGC p.Leu694_Thr698delinsPro disruptive_inframe_deletion, synonymous_variant 19/284 ENSP00000413354.2 C9JYS6
EGFRENST00000700145.1 linkc.585_598delATTAAGAGAAGCAAinsGC p.Leu196_Thr200delinsPro disruptive_inframe_deletion, synonymous_variant 6/9 ENSP00000514824.1 A0A8V8TPW8

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: drug response
Submissions summary: Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Tyrosine kinase inhibitor response Other:1
drug response, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJul 23, 2012- Responsive

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: rs727504257; hg19: chr7-55242468; COSMIC: COSV51803491; COSMIC: COSV51803491; API