rs1554530665
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016203.4(PRKAG2):c.622T>A(p.Ser208Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. S208F) has been classified as Uncertain significance.
Frequency
Consequence
NM_016203.4 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 |
---|---|---|---|---|---|---|---|
PRKAG2 | NM_016203.4 | c.622T>A | p.Ser208Thr | missense_variant | 4/16 | ENST00000287878.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAG2 | ENST00000287878.9 | c.622T>A | p.Ser208Thr | missense_variant | 4/16 | 1 | NM_016203.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Lethal congenital glycogen storage disease of heart Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2017 | 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 PRKAG2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 208 of the PRKAG2 protein (p.Ser208Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 11, 2023 | The p.S208T variant (also known as c.622T>A), located in coding exon 4 of the PRKAG2 gene, results from a T to A substitution at nucleotide position 622. The serine at codon 208 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at