7-151781368-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_016203.4(PRKAG2):c.250C>T(p.Arg84Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000905 in 1,613,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R84Q) has been classified as Likely benign.
Frequency
Consequence
NM_016203.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAG2 | NM_016203.4 | c.250C>T | p.Arg84Trp | missense_variant | 3/16 | ENST00000287878.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAG2 | ENST00000287878.9 | c.250C>T | p.Arg84Trp | missense_variant | 3/16 | 1 | NM_016203.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000499 AC: 76AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000147 AC: 36AN: 244326Hom.: 0 AF XY: 0.000120 AC XY: 16AN XY: 133066
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1460718Hom.: 0 Cov.: 33 AF XY: 0.0000399 AC XY: 29AN XY: 726624
GnomAD4 genome AF: 0.000499 AC: 76AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74464
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | PRKAG2: BS1 - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 31, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Arg84Trp varian t in PRKAG2 has not been reported in individuals with cardiomyopathy, but has be en identified in 0.2% (11/4402) of African American chromosomes by the NHLBI Exo me Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs61746358). Arg inine (Arg) at position 84 is not conserved in mammals or across evolutionarily distant species, and additional computational analyses (biochemical amino acid p roperties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Although this data supports that the Arg84Trp variant may be benign, additional studies are needed to fully assess its clinica l significance. - |
Cardiomyopathy Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 07, 2017 | - - |
PRKAG2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2019 | 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. - |
Lethal congenital glycogen storage disease of heart Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at