rs17848595

Variant names:

• chr1-56692378-G-A
• rs17848595
• NM_006252.4:c.351G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006252.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	NM_006252.4	MANE Select	c.351G>A	p.Arg117Arg	synonymous	Exon 4 of 9	NP_006243.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	ENST00000371244.9	TSL:1 MANE Select	c.351G>A	p.Arg117Arg	synonymous	Exon 4 of 9	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16442 AN: 151962 Hom.: 1300 Cov.: 31

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

GnomAD2 exomes AF: 0.0939 AC: 23588 AN: 251186 AF XY: 0.0966

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 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.: 31 AF XY: 0.0692 AC XY: 50312 AN XY: 727112

African (AFR) AF: 0.209 AC: 6974 AN: 33446

American (AMR) AF: 0.0428 AC: 1915 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 1338 AN: 26132

East Asian (EAS) AF: 0.235 AC: 9307 AN: 39688

South Asian (SAS) AF: 0.192 AC: 16534 AN: 86204

European-Finnish (FIN) AF: 0.0713 AC: 3808 AN: 53416

Middle Eastern (MID) AF: 0.117 AC: 676 AN: 5768

European-Non Finnish (NFE) AF: 0.0452 AC: 50311 AN: 1111912

Other (OTH) AF: 0.0821 AC: 4956 AN: 60380

GnomAD4 genome AF: 0.108 AC: 16486 AN: 152080 Hom.: 1306 Cov.: 31 AF XY: 0.112 AC XY: 8309 AN XY: 74364

African (AFR) AF: 0.204 AC: 8439 AN: 41438

American (AMR) AF: 0.0719 AC: 1100 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1253 AN: 5158

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4812

European-Finnish (FIN) AF: 0.0740 AC: 784 AN: 10598

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0501 AC: 3409 AN: 68002

Other (OTH) AF: 0.109 AC: 229 AN: 2108

Alfa AF: 0.0707 Hom.: 372

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.7
DANN	Benign	0.55
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17848595; hg19: chr1-57158051; COSMIC: COSV64802070;