chr7-55156802-G-T

Variant names:

• chr7-55156802-G-T
• NM_005228.5:c.1177G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005228.5(EGFR):​c.1177G>T​(p.Asp393Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EGFR NM_005228.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1177G>T	p.Asp393Tyr	missense_variant	Exon 10 of 28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1177G>T	p.Asp393Tyr	missense_variant	Exon 10 of 28	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D;.;D;.;.;D;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.2	.;M;.;M;M;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.3	D;D;.;D;D;D;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0080	D;D;.;D;D;D;.
Sift4G	Uncertain	0.012	D;D;D;D;D;D;.
Polyphen		0.97	D;P;.;D;B;P;.
Vest4		0.49
MutPred		0.53		.;Loss of disorder (P = 0.0475);.;Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);.;
MVP		0.90
MPC		1.5
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.43
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-55224495;