rs2395833

Variant names:

• chr7-107046003-G-T
• rs2395833
• NM_002736.3:c.307+789G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002736.3(PRKAR2B):​c.307+789G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,000 control chromosomes in the GnomAD database, including 8,210 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 0.32 (8210 hom., cov: 32)
• Consequence: PRKAR2B NM_002736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	NM_002736.3	MANE Select	c.307+789G>T		intron	N/A	NP_002727.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	ENST00000265717.5	TSL:1 MANE Select	c.307+789G>T		intron	N/A	ENSP00000265717.4	P31323
	PRKAR2B	ENST00000854598.1		c.307+789G>T		intron	N/A	ENSP00000524657.1
	PRKAR2B	ENST00000913925.1		c.307+789G>T		intron	N/A	ENSP00000583984.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49035 AN: 151880 Hom.: 8225 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.323 AC: 49035 AN: 152000 Hom.: 8210 Cov.: 32 AF XY: 0.330 AC XY: 24508 AN XY: 74280

African (AFR) AF: 0.242 AC: 10042 AN: 41464

American (AMR) AF: 0.415 AC: 6335 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3464

East Asian (EAS) AF: 0.461 AC: 2379 AN: 5164

South Asian (SAS) AF: 0.437 AC: 2108 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3858 AN: 10546

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21912 AN: 67954

Other (OTH) AF: 0.368 AC: 777 AN: 2112

Alfa AF: 0.324 Hom.: 15425

Bravo AF: 0.320

Asia WGS AF: 0.425 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2395833; hg19: chr7-106686448;