Variant rs17848595 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006252.4(PRKAA2):c.351G>A(p.Arg117Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 1,613,724 control chromosomes in the GnomAD database, including 6,665 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 0.11 ( 1306 hom., cov: 31)

Exomes 𝑓: 0.066 ( 5359 hom. )

Consequence

PRKAA2
NM_006252.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.261

Variant links:

Genes affected

PRKAA2 (HGNC:9377): (protein kinase AMP-activated catalytic subunit alpha 2) The protein encoded by this gene is a catalytic subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq, Jul 2008]

PRKAA2 links:

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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=-0.46).

BP7

Synonymous conserved (PhyloP=0.261 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA2	NM_006252.4 linkuse as main transcript	c.351G>A	p.Arg117Arg	synonymous_variant	4/9	ENST00000371244.9	NP_006243.2	P54646
PRKAA2	XM_017001693.2 linkuse as main transcript	c.81G>A	p.Arg27Arg	synonymous_variant	4/9		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9 linkuse as main transcript	c.351G>A	p.Arg117Arg	synonymous_variant	4/9	1	NM_006252.4	ENSP00000360290.4		P54646

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16442

AN:

151962

Hom.:

1300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0718

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.0740

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0501

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.0939

AC:

23588

AN:

251186

Hom.:

1858

AF XY:

0.0966

AC XY:

13110

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.0405

Gnomad ASJ exome

AF:

0.0536

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.0709

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0813

GnomAD4 exome

AF:

0.0656

AC:

95819

AN:

1461644

Hom.:

5359

Cov.:

AF XY:

0.0692

AC XY:

50312

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0428

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.0713

Gnomad4 NFE exome

AF:

0.0452

Gnomad4 OTH exome

AF:

0.0821

GnomAD4 genome

AF:

0.108

AC:

16486

AN:

152080

Hom.:

1306

Cov.:

AF XY:

0.112

AC XY:

8309

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.0719

Gnomad4 ASJ

AF:

0.0507

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.0740

Gnomad4 NFE

AF:

0.0501

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.0701

Hom.:

290

Bravo

AF:

0.111

Asia WGS

AF:

0.234

AC:

810

AN:

3478

EpiCase

AF:

0.0551

EpiControl

AF:

0.0542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.7

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over