1-56665650-C-T

Variant names:

• chr1-56665650-C-T
• rs2796516
• NM_006252.4:c.95-8731C>T

Variant summary

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

The NM_006252.4(PRKAA2):​c.95-8731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,086 control chromosomes in the GnomAD database, including 4,039 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 0.21 (4039 hom., cov: 32)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 7 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 (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.95-8731C>T		intron_variant	Intron 1 of 8	ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.-176-8731C>T		intron_variant	Intron 1 of 8		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.95-8731C>T		intron_variant	Intron 1 of 8	1	NM_006252.4	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32627 AN: 151968 Hom.: 4031 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.215 AC: 32668 AN: 152086 Hom.: 4039 Cov.: 32 AF XY: 0.219 AC XY: 16316 AN XY: 74354

African (AFR) AF: 0.285 AC: 11839 AN: 41482

American (AMR) AF: 0.170 AC: 2603 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2056 AN: 5150

South Asian (SAS) AF: 0.458 AC: 2206 AN: 4820

European-Finnish (FIN) AF: 0.166 AC: 1759 AN: 10578

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11105 AN: 67990

Other (OTH) AF: 0.201 AC: 424 AN: 2110

Alfa AF: 0.192 Hom.: 2358

Bravo AF: 0.212

Asia WGS AF: 0.383 AC: 1329 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	2.0
DANN	Benign	0.54
PhyloP100		-0.11
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: rs2796516; hg19: chr1-57131323;