7-55020559-TACACACACACACAC-TACACACACACACACACACACAC

Variant names:

• chr7-55020559-T-TACACACAC
• rs11568315
• NM_005228.5:c.88+1221_88+1228dupACACACAC

Variant summary

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

The NM_005228.5(EGFR):​c.88+1221_88+1228dupACACACAC 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 0.22 (3686 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: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.88+1221_88+1228dupACACACAC		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.88+1221_88+1228dupACACACAC		intron	N/A	NP_001333828.1
	EGFR	NM_001346898.2		c.88+1221_88+1228dupACACACAC		intron	N/A	NP_001333827.1	E7BSV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.88+1194_88+1195insACACACAC		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.88+1194_88+1195insACACACAC		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000344576.7	TSL:1	c.88+1194_88+1195insACACACAC		intron	N/A	ENSP00000345973.2	P00533-3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 31301 AN: 144896 Hom.: 3687 Cov.: 0

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.200

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: 0.216 AC: 31301 AN: 144984 Hom.: 3686 Cov.: 0 AF XY: 0.221 AC XY: 15560 AN XY: 70270

African (AFR) AF: 0.140 AC: 5481 AN: 39184

American (AMR) AF: 0.247 AC: 3619 AN: 14680

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 705 AN: 3362

East Asian (EAS) AF: 0.534 AC: 2591 AN: 4850

South Asian (SAS) AF: 0.257 AC: 1141 AN: 4440

European-Finnish (FIN) AF: 0.304 AC: 2865 AN: 9412

Middle Eastern (MID) AF: 0.138 AC: 39 AN: 282

European-Non Finnish (NFE) AF: 0.216 AC: 14220 AN: 65872

Other (OTH) AF: 0.198 AC: 402 AN: 2030

Alfa AF: 0.162 Hom.: 145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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; COSMIC: COSV51775315;