chr2-177230918-A-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_006164.5(NFE2L2):c.1685T>G(p.Leu562Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L562L) has been classified as Likely benign.
Frequency
Consequence
NM_006164.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFE2L2 | NM_006164.5 | c.1685T>G | p.Leu562Arg | missense_variant | 5/5 | ENST00000397062.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFE2L2 | ENST00000397062.8 | c.1685T>G | p.Leu562Arg | missense_variant | 5/5 | 1 | NM_006164.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249324Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135264
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461734Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727136
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74328
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 562 of the NFE2L2 protein (p.Leu562Arg). This variant is present in population databases (rs367873142, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with NFE2L2-related conditions. 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 NFE2L2 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. - |
NFE2L2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 15, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at