Variant 1-56674397-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_006252.4(PRKAA2):c.111A>G(p.Leu37Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,559,532 control chromosomes in the GnomAD database, including 1,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.025 ( 71 hom., cov: 33)

Exomes 𝑓: 0.035 ( 995 hom. )

Consequence

PRKAA2
NM_006252.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.48

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 1-56674397-A-G is Benign according to our data. Variant chr1-56674397-A-G is described in ClinVar as [Benign]. Clinvar id is 3056337.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0249 (3790/152196) while in subpopulation NFE AF= 0.0372 (2529/67954). AF 95% confidence interval is 0.036. There are 71 homozygotes in gnomad4. There are 1840 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3790 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA2	NM_006252.4 linkuse as main transcript	c.111A>G	p.Leu37Leu	synonymous_variant	2/9	ENST00000371244.9	NP_006243.2	P54646
PRKAA2	XM_017001693.2 linkuse as main transcript	c.-160A>G		5_prime_UTR_premature_start_codon_gain_variant	2/9		XP_016857182.1
PRKAA2	XM_017001693.2 linkuse as main transcript	c.-160A>G		5_prime_UTR_variant	2/9		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9 linkuse as main transcript	c.111A>G	p.Leu37Leu	synonymous_variant	2/9	1	NM_006252.4	ENSP00000360290.4		P54646

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3792

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00712

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0191

Gnomad FIN

AF:

0.0284

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0372

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0268

AC:

5591

AN:

208508

Hom.:

AF XY:

0.0278

AC XY:

3165

AN XY:

113962

show subpopulations

Gnomad AFR exome

AF:

0.00604

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0301

Gnomad EAS exome

AF:

0.000201

Gnomad SAS exome

AF:

0.0217

Gnomad FIN exome

AF:

0.0300

Gnomad NFE exome

AF:

0.0358

Gnomad OTH exome

AF:

0.0311

GnomAD4 exome

AF:

0.0345

AC:

48595

AN:

1407336

Hom.:

995

Cov.:

AF XY:

0.0342

AC XY:

23900

AN XY:

699300

show subpopulations

Gnomad4 AFR exome

AF:

0.00651

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.0287

Gnomad4 EAS exome

AF:

0.0000534

Gnomad4 SAS exome

AF:

0.0231

Gnomad4 FIN exome

AF:

0.0309

Gnomad4 NFE exome

AF:

0.0381

Gnomad4 OTH exome

AF:

0.0339

GnomAD4 genome

AF:

0.0249

AC:

3790

AN:

152196

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1840

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00708

Gnomad4 AMR

AF:

0.0247

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0193

Gnomad4 FIN

AF:

0.0284

Gnomad4 NFE

AF:

0.0372

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0321

Hom.:

Bravo

AF:

0.0236

Asia WGS

AF:

0.00783

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRKAA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.1

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over