7-55019290-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005228.5(EGFR):ā€‹c.13G>Cā€‹(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,355,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000022 ( 0 hom. )

Consequence

EGFR
NM_005228.5 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0970
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21666884).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EGFRNM_005228.5 linkuse as main transcriptc.13G>C p.Gly5Arg missense_variant 1/28 ENST00000275493.7 NP_005219.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EGFRENST00000275493.7 linkuse as main transcriptc.13G>C p.Gly5Arg missense_variant 1/281 NM_005228.5 ENSP00000275493 P1P00533-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000221
AC:
3
AN:
1355196
Hom.:
0
Cov.:
30
AF XY:
0.00000149
AC XY:
1
AN XY:
671944
show subpopulations
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:
0.00000284
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000848
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

EGFR-related lung cancer Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 27, 2024This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 5 of the EGFR protein (p.Gly5Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EGFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1477158). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T;.;T;.;.;T
Eigen
Benign
-0.99
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.66
T;T;T;T;T;T
M_CAP
Pathogenic
0.97
D
MetaRNN
Benign
0.22
T;T;T;T;T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.4
.;L;.;L;L;L
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
0.56
N;N;.;N;N;N
REVEL
Benign
0.16
Sift
Benign
0.051
T;T;.;D;T;D
Sift4G
Benign
0.28
T;T;T;D;T;T
Polyphen
0.027
B;B;.;B;B;B
Vest4
0.095
MutPred
0.30
Gain of MoRF binding (P = 0.0019);Gain of MoRF binding (P = 0.0019);Gain of MoRF binding (P = 0.0019);Gain of MoRF binding (P = 0.0019);Gain of MoRF binding (P = 0.0019);Gain of MoRF binding (P = 0.0019);
MVP
0.78
MPC
0.63
ClinPred
0.11
T
GERP RS
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.077
gMVP
0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774487133; hg19: chr7-55086983; API