Variant rs727504402 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005228.5(EGFR):c.2236_2252delinsAT(p.Glu746_Thr751delinsIle) variant causes a protein altering 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 protein_altering

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]

EGFR links:

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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
EGFR	NM_005228.5 linkuse as main transcript	c.2236_2252delinsAT	p.Glu746_Thr751delinsIle	protein_altering_variant	19/28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.2236_2252delinsAT	p.Glu746_Thr751delinsIle	protein_altering_variant	19/28	1	NM_005228.5	ENSP00000275493	P1	P00533-1
EGFR	ENST00000455089.5 linkuse as main transcript	c.2101_2117delinsAT	p.Glu701_Thr706delinsIle	protein_altering_variant	18/26	1		ENSP00000415559
EGFR	ENST00000450046.2 linkuse as main transcript	c.2077_2093delinsAT	p.Glu693_Thr698delinsIle	protein_altering_variant	19/28	4		ENSP00000413354
EGFR	ENST00000700145.1 linkuse as main transcript	c.585_601delinsAT	p.Glu196_Thr201delinsIle	protein_altering_variant	6/9			ENSP00000514824

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 28, 2010

- Likely 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.