7-107122773-G-A

Variant names:

• chr7-107122773-G-A
• rs13224682
• NM_002736.3:c.396+769G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002736.3(PRKAR2B):​c.396+769G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 152,294 control chromosomes in the GnomAD database, including 68,451 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 0.95 (68451 hom., cov: 31)
• Consequence: PRKAR2B NM_002736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 20 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]

PRKAR2B-AS1 (HGNC:40472): (PRKAR2B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAR2B	NM_002736.3	c.396+769G>A		intron_variant	Intron 3 of 10	ENST00000265717.5	NP_002727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAR2B	ENST00000265717.5	c.396+769G>A		intron_variant	Intron 3 of 10	1	NM_002736.3	ENSP00000265717.4

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144170 AN: 152176 Hom.: 68390 Cov.: 31

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.947 AC: 144292 AN: 152294 Hom.: 68451 Cov.: 31 AF XY: 0.949 AC XY: 70620 AN XY: 74450

African (AFR) AF: 0.985 AC: 40937 AN: 41566

American (AMR) AF: 0.955 AC: 14591 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3108 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5183 AN: 5188

South Asian (SAS) AF: 0.966 AC: 4667 AN: 4832

European-Finnish (FIN) AF: 0.940 AC: 9979 AN: 10618

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62742 AN: 68012

Other (OTH) AF: 0.947 AC: 2004 AN: 2116

Alfa AF: 0.932 Hom.: 147652

Bravo AF: 0.949

Asia WGS AF: 0.987 AC: 3431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.72
PhyloP100		-0.12
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: rs13224682; hg19: chr7-106763218;