7-55019297-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005228.5(EGFR):c.20C>A(p.Ala7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,360,766 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7P) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.20C>A | p.Ala7Asp | missense_variant | 1/28 | ENST00000275493.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.20C>A | p.Ala7Asp | missense_variant | 1/28 | 1 | NM_005228.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000294 AC: 4AN: 1360766Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1AN XY: 675100
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
EGFR-related lung cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 26, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with EGFR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 7 of the EGFR protein (p.Ala7Asp). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at