dbSNP rs3738568: PRKAA2:c.*205A>G (chr1-56707918-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006252.4(PRKAA2):c.*205A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 597,550 control chromosomes in the GnomAD database, including 797 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 0.028 ( 115 hom., cov: 32)

Exomes 𝑓: 0.040 ( 682 hom. )

Consequence

PRKAA2
NM_006252.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Publications

6 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA2	NM_006252.4 link	c.*205A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000371244.9	NP_006243.2	P54646
PRKAA2	XM_017001693.2 link	c.*205A>G		3_prime_UTR_variant	Exon 9 of 9		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9 link	c.*205A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_006252.4	ENSP00000360290.4		P54646

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4229

AN:

152178

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00586

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0222

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.0438

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0278

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.0398

AC:

17723

AN:

445254

Hom.:

682

Cov.:

AF XY:

0.0422

AC XY:

9902

AN XY:

234646

show subpopulations

African (AFR)

AF:

0.00550

AC:

AN:

12354

American (AMR)

AF:

0.0120

AC:

197

AN:

16484

Ashkenazi Jewish (ASJ)

AF:

0.0319

AC:

423

AN:

13252

East Asian (EAS)

AF:

0.135

AC:

4003

AN:

29604

South Asian (SAS)

AF:

0.0887

AC:

3780

AN:

42636

European-Finnish (FIN)

AF:

0.0383

AC:

1055

AN:

27510

Middle Eastern (MID)

AF:

0.0167

AC:

AN:

1918

European-Non Finnish (NFE)

AF:

0.0268

AC:

7391

AN:

276118

Other (OTH)

AF:

0.0305

AC:

774

AN:

25378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

799

1598

2398

3197

3996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0278

AC:

4233

AN:

152296

Hom.:

115

Cov.:

AF XY:

0.0305

AC XY:

2269

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00585

AC:

243

AN:

41572

American (AMR)

AF:

0.0224

AC:

343

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3470

East Asian (EAS)

AF:

0.121

AC:

627

AN:

5178

South Asian (SAS)

AF:

0.0995

AC:

480

AN:

4824

European-Finnish (FIN)

AF:

0.0438

AC:

465

AN:

10606

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0278

AC:

1891

AN:

68036

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

205

410

615

820

1025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0240

Hom.:

Bravo

AF:

0.0231

Asia WGS

AF:

0.0920

AC:

320

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.10

(source)

DANN

Benign

0.61

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over