rs759393540
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_016203.4(PRKAG2):c.945A>G(p.Val315=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,447,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V315V) has been classified as Uncertain significance.
Frequency
Consequence
NM_016203.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAG2 | NM_016203.4 | c.945A>G | p.Val315= | splice_region_variant, synonymous_variant | 7/16 | ENST00000287878.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAG2 | ENST00000287878.9 | c.945A>G | p.Val315= | splice_region_variant, synonymous_variant | 7/16 | 1 | NM_016203.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250362Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135314
GnomAD4 exome AF: 0.0000152 AC: 22AN: 1447522Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8AN XY: 720900
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Lethal congenital glycogen storage disease of heart Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2022 | 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 sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 260698). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. This variant is present in population databases (rs759393540, gnomAD 0.02%). This sequence change affects codon 315 of the PRKAG2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PRKAG2 protein. It affects a nucleotide within the consensus splice site. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at