1-56677306-T-C

Variant names:

• chr1-56677306-T-C
• rs2796495
• NM_006252.4:c.236+2784T>C

Variant summary

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

The NM_006252.4(PRKAA2):​c.236+2784T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,034 control chromosomes in the GnomAD database, including 17,517 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 0.48 (17517 hom., cov: 33)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	NM_006252.4	MANE Select	c.236+2784T>C		intron	N/A	NP_006243.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	ENST00000371244.9	TSL:1 MANE Select	c.236+2784T>C		intron	N/A	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72292 AN: 151916 Hom.: 17487 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.476 AC: 72361 AN: 152034 Hom.: 17517 Cov.: 33 AF XY: 0.480 AC XY: 35652 AN XY: 74312

African (AFR) AF: 0.436 AC: 18094 AN: 41480

American (AMR) AF: 0.592 AC: 9040 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1486 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3299 AN: 5142

South Asian (SAS) AF: 0.557 AC: 2679 AN: 4814

European-Finnish (FIN) AF: 0.460 AC: 4869 AN: 10578

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31421 AN: 67954

Other (OTH) AF: 0.471 AC: 996 AN: 2114

Alfa AF: 0.469 Hom.: 2209

Bravo AF: 0.485

Asia WGS AF: 0.573 AC: 1993 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.44
PhyloP100		-0.33
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: rs2796495; hg19: chr1-57142979;