NM_006252.4:c.476-577A>G

Variant names:

• chr1-56693188-A-G
• rs2143754
• NM_006252.4:c.476-577A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006252.4(PRKAA2):​c.476-577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,974 control chromosomes in the GnomAD database, including 22,086 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 0.53 (22086 hom., cov: 32)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.476-577A>G		intron_variant	Intron 4 of 8	ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.206-577A>G		intron_variant	Intron 4 of 8		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.476-577A>G		intron_variant	Intron 4 of 8	1	NM_006252.4	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80951 AN: 151858 Hom.: 22056 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.533 AC: 81013 AN: 151974 Hom.: 22086 Cov.: 32 AF XY: 0.528 AC XY: 39248 AN XY: 74288

African (AFR) AF: 0.635 AC: 26339 AN: 41476

American (AMR) AF: 0.409 AC: 6247 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2107 AN: 5172

South Asian (SAS) AF: 0.441 AC: 2125 AN: 4818

European-Finnish (FIN) AF: 0.507 AC: 5342 AN: 10540

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35092 AN: 67908

Other (OTH) AF: 0.541 AC: 1142 AN: 2110

Alfa AF: 0.541 Hom.: 3809

Bravo AF: 0.530

Asia WGS AF: 0.453 AC: 1572 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.46
PhyloP100		-1.0
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: rs2143754; hg19: chr1-57158861; COSMIC: COSV64802960;