rs727503014

chr7-55174766-TATCAAGGAATTAAGAGAAGC-TGTCAA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_005228.5(EGFR):c.2230_2249delinsGTCAA(p.Ile744_Ala750delinsValLys) variant causes a protein altering change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as drug response (★). Synonymous variant affecting the same amino acid position (i.e. IKELREA744IK) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFR NM_005228.5 protein_altering
• Clinical Significance: drug response criteria provided, single submitter O:1
• Conservation: PhyloP100: 9.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2230_2249delinsGTCAA	p.Ile744_Ala750delinsValLys	protein_altering_variant	19/28	ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2230_2249delinsGTCAA	p.Ile744_Ala750delinsValLys	protein_altering_variant	19/28	1	NM_005228.5	P1
EGFR	ENST00000455089.5	c.2095_2114delinsGTCAA	p.Ile699_Ala705delinsValLys	protein_altering_variant	18/26	1
EGFR	ENST00000450046.2	c.2071_2090delinsGTCAA	p.Ile691_Ala697delinsValLys	protein_altering_variant	19/28	4
EGFR	ENST00000700145.1	c.579_598delinsGTCAA	p.Ile194_Ala200delinsValLys	protein_altering_variant	6/9

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

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

Mar 30, 2010

- Likely Responsive

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs727503014; hg19: chr7-55242460; COSMIC: COSV51850584; COSMIC: COSV51850584;