rs760826751
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_016203.4(PRKAG2):āc.1114G>Cā(p.Asp372His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D372N) has been classified as Uncertain significance.
Frequency
Consequence
NM_016203.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAG2 | NM_016203.4 | c.1114G>C | p.Asp372His | missense_variant | 11/16 | ENST00000287878.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAG2 | ENST00000287878.9 | c.1114G>C | p.Asp372His | missense_variant | 11/16 | 1 | NM_016203.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251332Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135850
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461498Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727072
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | May 31, 2023 | - - |
Lethal congenital glycogen storage disease of heart Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2021 | This variant has not been reported in the literature in individuals with PRKAG2-related conditions. 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. 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 expected to disrupt PRKAG2 protein function. This variant is present in population databases (rs760826751, ExAC 0.001%). This sequence change replaces aspartic acid with histidine at codon 372 of the PRKAG2 protein (p.Asp372His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at