rs182084936
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_016203.4(PRKAG2):c.617C>T(p.Pro206Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,190 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_016203.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKAG2 | NM_016203.4 | c.617C>T | p.Pro206Leu | missense_variant | 4/16 | ENST00000287878.9 | NP_057287.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKAG2 | ENST00000287878.9 | c.617C>T | p.Pro206Leu | missense_variant | 4/16 | 1 | NM_016203.4 | ENSP00000287878.3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251382Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727246
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74478
ClinVar
Submissions by phenotype
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 04, 2022 | This missense variant replaces proline with leucine at codon 206 of the PRKAG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/282752 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 23, 2017 | Variant summary: The PRKAG2 c.617C>T (p.Pro206Leu) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 2/121060 control chromosomes at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic PRKAG2 variant (0.000025). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. - |
Wolff-Parkinson-White pattern;C1833236:Hypertrophic cardiomyopathy 6;C1849813:Lethal congenital glycogen storage disease of heart Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 26, 2024 | - - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 05, 2022 | This missense variant replaces proline with leucine at codon 206 of the PRKAG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/282752 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Lethal congenital glycogen storage disease of heart Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 14, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at