rs28929495
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2_SupportingPM5PP3_Strong
The NM_005228(EGFR):c.2155G>A(p.Gly719Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance,drug response (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G719C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005228 missense
Scores
Clinical Significance
Conservation
Links
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.2155G>A | p.Gly719Ser | missense_variant | 18/28 | ENST00000275493.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.2155G>A | p.Gly719Ser | missense_variant | 18/28 | 1 | NM_005228.5 | P1 | |
EGFR | ENST00000455089.5 | c.2020G>A | p.Gly674Ser | missense_variant | 17/26 | 1 | |||
EGFR | ENST00000450046.2 | c.1996G>A | p.Gly666Ser | missense_variant | 18/28 | 4 | |||
EGFR | ENST00000700145.1 | c.505G>A | p.Gly169Ser | missense_variant | 5/9 |
Frequencies
GnomAD3 genomesCov.: 33
ClinVar
Submissions by phenotype
Non-small cell lung carcinoma Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Jul 14, 2015 | - - |
EGFR-related lung cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2021 | This sequence change replaces glycine with serine at codon 719 of the EGFR protein (p.Gly719Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant is a common somatic change in non-small cell lung cancer (NSCLC) (PMID: 29100434, 25061320, 23468066, 24039832). While this variant has been reported in the literature, it has not been reported in the germline of individuals with EGFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 16612). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in, somatic Other:1
drug response, no assertion criteria provided | literature only | OMIM | Jun 04, 2004 | - - |
Tyrosine kinase inhibitor response Other:1
drug response, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 20, 2012 | - Responsive |
Neoplasm of the large intestine Other:1
not provided, no assertion provided | literature only | Database of Curated Mutations (DoCM) | Mar 10, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at