7-55174772-GGAATTAAGAGAAGCAAC-GCA

Position:

• chr7-55174772-GGAATTAAGAGAAGCAAC-GCA

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_005228.5(EGFR):​c.2236_2252delinsCA​(p.Glu746_Thr751delinsGln) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFR NM_005228.5 protein_altering
• Clinical Significance: Not reported in ClinVar
• 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 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	c.2236_2252delinsCA	p.Glu746_Thr751delinsGln	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	c.2236_2252delinsCA	p.Glu746_Thr751delinsGln	protein_altering_variant	19/28	1	NM_005228.5	ENSP00000275493	P1
EGFR	ENST00000455089.5	c.2101_2117delinsCA	p.Glu701_Thr706delinsGln	protein_altering_variant	18/26	1		ENSP00000415559
EGFR	ENST00000450046.2	c.2077_2093delinsCA	p.Glu693_Thr698delinsGln	protein_altering_variant	19/28	4		ENSP00000413354
EGFR	ENST00000700145.1	c.585_601delinsCA	p.Glu196_Thr201delinsGln	protein_altering_variant	6/9			ENSP00000514824

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-55242466; COSMIC: COSV51792545; COSMIC: COSV51792545;