chr7-55191741-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5
The NM_005228.5(EGFR):c.2492G>A(p.Arg831His) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R831C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005228.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.2492G>A | p.Arg831His | missense_variant | 21/28 | ENST00000275493.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.2492G>A | p.Arg831His | missense_variant | 21/28 | 1 | NM_005228.5 | P1 | |
EGFR | ENST00000455089.5 | c.2357G>A | p.Arg786His | missense_variant | 20/26 | 1 | |||
EGFR | ENST00000450046.2 | c.2333G>A | p.Arg778His | missense_variant | 21/28 | 4 | |||
EGFR | ENST00000700145.1 | c.842G>A | p.Arg281His | missense_variant | 8/9 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251116Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135712
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461734Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727174
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74272
ClinVar
Submissions by phenotype
Squamous cell lung carcinoma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | 3DMed Clinical Laboratory Inc | Sep 06, 2017 | - - |
Lung adenocarcinoma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | 3DMed Clinical Laboratory Inc | Sep 06, 2017 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 06, 2021 | - - |
EGFR-related lung cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 831 of the EGFR protein (p.Arg831His). This variant is present in population databases (rs150036236, gnomAD 0.02%). This missense change has been observed in individual(s) with lung cancer or prostate cancer or isolated hypogonadotropic hypogonadism (PMID: 30098700, 30610926, 31721094, 32978518). ClinVar contains an entry for this variant (Variation ID: 560007). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on EGFR function (PMID: 20942962, 25382819, 27294619, 32978518). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 18, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at