1-56676026-T-C

Variant names:

• chr1-56676026-T-C
• rs715405
• NM_006252.4:c.236+1504T>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+1504T>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 152,024 control chromosomes in the GnomAD database, including 17,527 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 (17527 hom., cov: 32)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• Publications: 2 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 = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.236+1504T>C		intron_variant	Intron 2 of 8	ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.-35+1504T>C		intron_variant	Intron 2 of 8		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.236+1504T>C		intron_variant	Intron 2 of 8	1	NM_006252.4	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72311 AN: 151906 Hom.: 17497 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.476 AC: 72380 AN: 152024 Hom.: 17527 Cov.: 32 AF XY: 0.480 AC XY: 35663 AN XY: 74310

African (AFR) AF: 0.436 AC: 18077 AN: 41438

American (AMR) AF: 0.592 AC: 9039 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3311 AN: 5154

South Asian (SAS) AF: 0.557 AC: 2685 AN: 4818

European-Finnish (FIN) AF: 0.461 AC: 4866 AN: 10566

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

European-Non Finnish (NFE) AF: 0.462 AC: 31446 AN: 67992

Other (OTH) AF: 0.470 AC: 992 AN: 2110

Alfa AF: 0.467 Hom.: 2794

Bravo AF: 0.485

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.73
PhyloP100		-2.4
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: rs715405; hg19: chr1-57141699;