rs257376
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1
The NM_002736.3(PRKAR2B):c.1227G>A(p.Thr409=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,613,210 control chromosomes in the GnomAD database, including 221,514 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.51 ( 20158 hom., cov: 32)
Exomes 𝑓: 0.52 ( 201356 hom. )
Consequence
PRKAR2B
NM_002736.3 synonymous
NM_002736.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.576
Genes affected
PRKAR2B (HGNC:9392): (protein kinase cAMP-dependent type II regulatory subunit beta) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. This subunit has been shown to interact with and suppress the transcriptional activity of the cAMP responsive element binding protein 1 (CREB1) in activated T cells. Knockout studies in mice suggest that this subunit may play an important role in regulating energy balance and adiposity. The studies also suggest that this subunit may mediate the gene induction and cataleptic behavior induced by haloperidol. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP7
?
Synonymous conserved (PhyloP=0.576 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAR2B | NM_002736.3 | c.1227G>A | p.Thr409= | synonymous_variant | 11/11 | ENST00000265717.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR2B | ENST00000265717.5 | c.1227G>A | p.Thr409= | synonymous_variant | 11/11 | 1 | NM_002736.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.512 AC: 77798AN: 151888Hom.: 20138 Cov.: 32
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GnomAD3 exomes AF: 0.498 AC: 125280AN: 251346Hom.: 31661 AF XY: 0.498 AC XY: 67597AN XY: 135846
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GnomAD4 exome AF: 0.522 AC: 763443AN: 1461204Hom.: 201356 Cov.: 46 AF XY: 0.519 AC XY: 377550AN XY: 726956
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GnomAD4 genome ? AF: 0.512 AC: 77874AN: 152006Hom.: 20158 Cov.: 32 AF XY: 0.506 AC XY: 37587AN XY: 74296
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Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at