rs121913442

Positions:

• chr7-55174774-AATTAAGAGAAGCAAC-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_005228.5(EGFR):​c.2240_2254del​(p.Leu747_Thr751del) variant causes a inframe deletion 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 Likely pathogenic,drug response (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFR NM_005228.5 inframe_deletion
• Clinical Significance: Likely pathogenic; drug response no assertion criteria provided P:1 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 Likely_pathogenic. Variant got 6 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
• PP5: Variant 7-55174774-AATTAAGAGAAGCAAC-A is Pathogenic according to our data. Variant chr7-55174774-AATTAAGAGAAGCAAC-A is described in ClinVar as [Likely_pathogenic, drug_response]. Clinvar id is 177649.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2240_2254del	p.Leu747_Thr751del	inframe_deletion	19/28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2240_2254del	p.Leu747_Thr751del	inframe_deletion	19/28	1	NM_005228.5	ENSP00000275493	P1
EGFR	ENST00000455089.5	c.2105_2119del	p.Leu702_Thr706del	inframe_deletion	18/26	1		ENSP00000415559
EGFR	ENST00000450046.2	c.2081_2095del	p.Leu694_Thr698del	inframe_deletion	19/28	4		ENSP00000413354
EGFR	ENST00000700145.1	c.589_603del	p.Leu197_Thr201del	inframe_deletion	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

Significance: Likely pathogenic; drug response

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Lung adenocarcinoma Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University

-

- -

Tyrosine kinase inhibitor response Other:1

drug response, no assertion criteria provided

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 28, 2006

- 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: rs121913442; hg19: chr7-55242467;