rs17289589
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005228.5(EGFR):c.293G>A(p.Arg98Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R98R) has been classified as Likely benign.
Frequency
Consequence
NM_005228.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.293G>A | p.Arg98Gln | missense_variant | 3/28 | ENST00000275493.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.293G>A | p.Arg98Gln | missense_variant | 3/28 | 1 | NM_005228.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000111 AC: 28AN: 251486Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135920
GnomAD4 exome AF: 0.0000862 AC: 126AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000866 AC XY: 63AN XY: 727240
GnomAD4 genome AF: 0.000112 AC: 17AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74494
ClinVar
Submissions by phenotype
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Nov 06, 2020 | ACMG classification criteria: BP4 - |
EGFR-related lung cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 98 of the EGFR protein (p.Arg98Gln). This variant is present in population databases (rs17289589, gnomAD 0.05%). 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: 859594). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EGFR protein function with a negative predictive value of 80%. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at