chr20-22582124-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021784.5(FOXA2):c.1118A>T(p.Glu373Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,443,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E373D) has been classified as Uncertain significance.
Frequency
Consequence
NM_021784.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXA2 | NM_021784.5 | c.1118A>T | p.Glu373Val | missense_variant | 2/2 | ENST00000419308.7 | |
FOXA2 | NM_153675.3 | c.1100A>T | p.Glu367Val | missense_variant | 3/3 | ||
FOXA2 | XM_047440133.1 | c.1100A>T | p.Glu367Val | missense_variant | 3/3 | ||
FOXA2 | XM_047440134.1 | c.1010A>T | p.Glu337Val | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXA2 | ENST00000419308.7 | c.1118A>T | p.Glu373Val | missense_variant | 2/2 | 1 | NM_021784.5 | P4 | |
FOXA2 | ENST00000377115.4 | c.1100A>T | p.Glu367Val | missense_variant | 3/3 | 1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000946 AC: 2AN: 211478Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 114144
GnomAD4 exome AF: 0.00000139 AC: 2AN: 1443564Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 716408
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 04, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 373 of the FOXA2 protein (p.Glu373Val). This variant is present in population databases (rs767212576, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FOXA2-related conditions. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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