chr1-56660977-C-T

Position:

• chr1-56660977-C-T

Variant summary

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

The NM_006252.4(PRKAA2):​c.95-13404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,898 control chromosomes in the GnomAD database, including 22,541 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 0.54 (22541 hom., cov: 31)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.95-13404C>T		intron_variant		ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.-176-13404C>T		intron_variant			XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.95-13404C>T		intron_variant		1	NM_006252.4	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81843 AN: 151780 Hom.: 22505 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.539 AC: 81932 AN: 151898 Hom.: 22541 Cov.: 31 AF XY: 0.545 AC XY: 40444 AN XY: 74228

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.531

Alfa AF: 0.484 Hom.: 5437

Bravo AF: 0.552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
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: rs2746349; hg19: chr1-57126650;