1-56698492-T-G

Variant names:

• chr1-56698492-T-G
• rs857155
• NM_006252.4:c.788+2333T>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.788+2333T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,006 control chromosomes in the GnomAD database, including 15,461 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 (15461 hom., cov: 32)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	NM_006252.4	MANE Select	c.788+2333T>G		intron	N/A	NP_006243.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	ENST00000371244.9	TSL:1 MANE Select	c.788+2333T>G		intron	N/A	ENSP00000360290.4	P54646
	PRKAA2	ENST00000860136.1		c.788+2333T>G		intron	N/A	ENSP00000530195.1
	PRKAA2	ENST00000860138.1		c.563+4640T>G		intron	N/A	ENSP00000530197.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66963 AN: 151888 Hom.: 15441 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.441 AC: 67003 AN: 152006 Hom.: 15461 Cov.: 32 AF XY: 0.446 AC XY: 33151 AN XY: 74306

African (AFR) AF: 0.315 AC: 13080 AN: 41466

American (AMR) AF: 0.576 AC: 8796 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3470

East Asian (EAS) AF: 0.591 AC: 3049 AN: 5160

South Asian (SAS) AF: 0.552 AC: 2663 AN: 4822

European-Finnish (FIN) AF: 0.470 AC: 4957 AN: 10554

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31571 AN: 67952

Other (OTH) AF: 0.433 AC: 913 AN: 2110

Alfa AF: 0.380 Hom.: 2043

Bravo AF: 0.443

Asia WGS AF: 0.533 AC: 1852 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.60
PhyloP100		-0.019
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: rs857155; hg19: chr1-57164165;