Variant chr7-55181299-T-TACCATC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4PP3

The NM_005228.5(EGFR):c.2292_2293insCATCAC(p.Tyr764_Val765insHisHis) variant causes a inframe insertion 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 (no stars). Synonymous variant affecting the same amino acid position (i.e. Y764Y) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Consequence

EGFR
NM_005228.5 inframe_insertion

Scores

Not classified

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 9.29

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:

EGFR-AS1 (HGNC:40207): (EGFR antisense RNA 1)

EGFR-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 15 uncertain in NM_005228.5

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	UniProt
EGFR	NM_005228.5 linkuse as main transcript	c.2292_2293insCATCAC	p.Tyr764_Val765insHisHis	inframe_insertion	20/28	ENST00000275493.7
EGFR-AS1	NR_047551.1 linkuse as main transcript	n.1271_1272insGATGGT		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.2292_2293insCATCAC	p.Tyr764_Val765insHisHis	inframe_insertion	20/28	1	NM_005228.5	P1	P00533-1
EGFR-AS1	ENST00000442411.2 linkuse as main transcript	n.1299_1300insGATGGT		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Tyrosine kinase inhibitor response

Other:1

drug response, no assertion criteria provided

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 01, 2008

- 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over