7-55201223-C-T

Variant names:

• chr7-55201223-C-T
• rs2293347
• NM_005228.5:c.2982C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005228.5(EGFR):​c.2982C>T​(p.Asp994Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,614,064 control chromosomes in the GnomAD database, including 13,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1060 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12175 hom.)
• Consequence: EGFR NM_005228.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.403
• Publications: 95 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-AS1 (HGNC:40207): (EGFR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-55201223-C-T is Benign according to our data. Variant chr7-55201223-C-T is described in ClinVar as Benign. ClinVar VariationId is 259679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.403 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

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.2982C>T	p.Asp994Asp	synonymous	Exon 25 of 28	NP_005219.2
	EGFR	NM_001346899.2		c.2847C>T	p.Asp949Asp	synonymous	Exon 24 of 27	NP_001333828.1
	EGFR	NM_001346900.2		c.2823C>T	p.Asp941Asp	synonymous	Exon 25 of 28	NP_001333829.1	C9JYS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2982C>T	p.Asp994Asp	synonymous	Exon 25 of 28	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.2847C>T	p.Asp949Asp	synonymous	Exon 24 of 26	ENSP00000415559.1	Q504U8
	EGFR	ENST00000898199.1		c.2973C>T	p.Asp991Asp	synonymous	Exon 25 of 28	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15164 AN: 152072 Hom.: 1057 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0936

GnomAD2 exomes AF: 0.137 AC: 34569 AN: 251492 AF XY: 0.141

Gnomad AFR exome AF: 0.0236

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.0731

Gnomad EAS exome AF: 0.272

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.0996

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.118 AC: 172092 AN: 1461874 Hom.: 12175 Cov.: 33 AF XY: 0.120 AC XY: 87503 AN XY: 727246

African (AFR) AF: 0.0212 AC: 711 AN: 33480

American (AMR) AF: 0.149 AC: 6660 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0742 AC: 1939 AN: 26136

East Asian (EAS) AF: 0.310 AC: 12322 AN: 39700

South Asian (SAS) AF: 0.224 AC: 19326 AN: 86256

European-Finnish (FIN) AF: 0.193 AC: 10291 AN: 53416

Middle Eastern (MID) AF: 0.0733 AC: 423 AN: 5768

European-Non Finnish (NFE) AF: 0.102 AC: 113251 AN: 1111998

Other (OTH) AF: 0.119 AC: 7169 AN: 60396

GnomAD4 genome AF: 0.0997 AC: 15168 AN: 152190 Hom.: 1060 Cov.: 32 AF XY: 0.109 AC XY: 8124 AN XY: 74402

African (AFR) AF: 0.0272 AC: 1129 AN: 41552

American (AMR) AF: 0.135 AC: 2059 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1449 AN: 5152

South Asian (SAS) AF: 0.234 AC: 1126 AN: 4806

European-Finnish (FIN) AF: 0.193 AC: 2042 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6800 AN: 68002

Other (OTH) AF: 0.0940 AC: 198 AN: 2106

Alfa AF: 0.0985 Hom.: 2941

Bravo AF: 0.0910

Asia WGS AF: 0.266 AC: 921 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	EGFR-related lung cancer (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Lung cancer (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2293347; hg19: chr7-55268916; COSMIC: COSV51772678; COSMIC: COSV51772678;