1-56646549-T-G

Position:

• chr1-56646549-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006252.4(PRKAA2):​c.94+1068T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,000 control chromosomes in the GnomAD database, including 16,488 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 0.46 (16488 hom., cov: 32)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAA2	NM_006252.4	c.94+1068T>G		intron_variant		ENST00000371244.9
PRKAA2	XM_017001693.2	c.-177+554T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAA2	ENST00000371244.9	c.94+1068T>G		intron_variant		1	NM_006252.4	P1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69767 AN: 151882 Hom.: 16482 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.459 AC: 69795 AN: 152000 Hom.: 16488 Cov.: 32 AF XY: 0.454 AC XY: 33709 AN XY: 74270

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.468

Alfa AF: 0.478 Hom.: 2207

Bravo AF: 0.448

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.5
DANN	Benign	0.69

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: rs1124900; hg19: chr1-57112222; COSMIC: COSV64802800; COSMIC: COSV64802800;