7-55020559-TACACACACACACAC-TACACACACACACACACAC

Variant names:

• chr7-55020559-T-TACAC
• rs11568315
• NM_005228.5:c.88+1225_88+1228dupACAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005228.5(EGFR):​c.88+1225_88+1228dupACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1679 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
• non-small cell lung carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• inflammatory skin and bowel disease, neonatal, 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neonatal inflammatory skin and bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+1225_88+1228dupACAC		intron_variant	Intron 1 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.88+1194_88+1195insACAC		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21041 AN: 144986 Hom.: 1676 Cov.: 0

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0205

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0752

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.124

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.145 AC: 21054 AN: 145076 Hom.: 1679 Cov.: 0 AF XY: 0.146 AC XY: 10301 AN XY: 70326

African (AFR) AF: 0.0730 AC: 2863 AN: 39222

American (AMR) AF: 0.196 AC: 2886 AN: 14694

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 366 AN: 3362

East Asian (EAS) AF: 0.0206 AC: 100 AN: 4864

South Asian (SAS) AF: 0.0715 AC: 319 AN: 4460

European-Finnish (FIN) AF: 0.216 AC: 2039 AN: 9422

Middle Eastern (MID) AF: 0.0775 AC: 22 AN: 284

European-Non Finnish (NFE) AF: 0.184 AC: 12103 AN: 65862

Other (OTH) AF: 0.124 AC: 252 AN: 2030

Alfa AF: 0.119 Hom.: 145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11568315; hg19: chr7-55088252;