dbSNP rs857148: PRKAA2:c.*1772A>C (chr1-56709485-A-C) – 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.*1772A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,936 control chromosomes in the GnomAD database, including 15,427 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 0.44 ( 15426 hom., cov: 32)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

PRKAA2
NM_006252.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.316

Publications

11 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:

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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=-0.63).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA2	NM_006252.4 link	c.*1772A>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2 link	c.*1772A>C		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.*1772A>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_006252.4	ENSP00000360290.4

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66875

AN:

151814

Hom.:

15406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.574

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.429

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.440

AC:

66914

AN:

151932

Hom.:

15426

Cov.:

AF XY:

0.446

AC XY:

33083

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.316

AC:

13090

AN:

41448

American (AMR)

AF:

0.574

AC:

8756

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1491

AN:

3470

East Asian (EAS)

AF:

0.591

AC:

3054

AN:

5168

South Asian (SAS)

AF:

0.552

AC:

2655

AN:

4814

European-Finnish (FIN)

AF:

0.470

AC:

4955

AN:

10548

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.464

AC:

31524

AN:

67920

Other (OTH)

AF:

0.433

AC:

913

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1865

3730

5595

7460

9325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.457

Hom.:

42586

Bravo

AF:

0.442

Asia WGS

AF:

0.538

AC:

1872

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.32

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over