rs587778248

chr7-55161534-C-Achr7-55161534-C-Gchr7-55161534-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005228.5(EGFR):c.1534C>A(p.Pro512Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P512S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: EGFR NM_005228.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05896586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.1534C>A	p.Pro512Thr	missense_variant	13/28	ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.1534C>A	p.Pro512Thr	missense_variant	13/28	1	NM_005228.5	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	0.19
Dann	Benign	0.39
DEOGEN2	Benign	0.20	T;.;T;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.82	T;D;T;T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.059	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.050	N;N;D;N;N;.
REVEL	Benign	0.014
Sift	Benign	0.27	T;T;D;T;T;.
Sift4G	Benign	0.56	T;T;T;T;T;.
Polyphen		0.0	B;B;.;B;B;.
Vest4		0.17
MutPred		0.34		.;Gain of catalytic residue at P512 (P = 0.0019);.;Gain of catalytic residue at P512 (P = 0.0019);Gain of catalytic residue at P512 (P = 0.0019);.;
MVP		0.43
MPC		0.58
ClinPred		0.13	T
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr7-55229227;