1-56676026-T-C

Position:

• chr1-56676026-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.236+1504T>C		intron_variant		ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.-35+1504T>C		intron_variant			XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.236+1504T>C		intron_variant		1	NM_006252.4	ENSP00000360290	P1

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

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.470

Alfa AF: 0.468 Hom.: 2719

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

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

Other links and lift over

dbSNP: rs715405; hg19: chr1-57141699;