rs201876556
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_016203.4(PRKAG2):c.897C>T(p.Asn299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,610,496 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000058 ( 1 hom. )
Consequence
PRKAG2
NM_016203.4 synonymous
NM_016203.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.729
Genes affected
PRKAG2 (HGNC:9386): (protein kinase AMP-activated non-catalytic subunit gamma 2) AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family. Mutations in this gene have been associated with Wolff-Parkinson-White syndrome, familial hypertrophic cardiomyopathy, and glycogen storage disease of the heart. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 7-151576420-G-A is Benign according to our data. Variant chr7-151576420-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 45737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.729 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000263 (4/152176) while in subpopulation SAS AF= 0.000414 (2/4832). AF 95% confidence interval is 0.0000729. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 84 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAG2 | NM_016203.4 | c.897C>T | p.Asn299= | synonymous_variant | 7/16 | ENST00000287878.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAG2 | ENST00000287878.9 | c.897C>T | p.Asn299= | synonymous_variant | 7/16 | 1 | NM_016203.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152176Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251052Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135684
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GnomAD4 exome AF: 0.0000576 AC: 84AN: 1458320Hom.: 1 Cov.: 30 AF XY: 0.0000730 AC XY: 53AN XY: 725766
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152176Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 15, 2015 | p.Asn299Asn in exon 7 of PRKAG2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 12/15416 South As ian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs201876556). - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 01, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2019 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
Lethal congenital glycogen storage disease of heart Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at