rs6671760

Positions:

• chr1-56674992-C-G
• chr1-56674992-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.236+470C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,740 control chromosomes in the GnomAD database, including 19,972 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 0.51 (19972 hom., cov: 33)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.236+470C>G		intron_variant		ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.-35+470C>G		intron_variant			XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.236+470C>G		intron_variant		1	NM_006252.4	ENSP00000360290	P1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77324 AN: 151622 Hom.: 19954 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.510 AC: 77368 AN: 151740 Hom.: 19972 Cov.: 33 AF XY: 0.506 AC XY: 37513 AN XY: 74138

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.511

Alfa AF: 0.504 Hom.: 2357

Bravo AF: 0.501

Asia WGS AF: 0.417 AC: 1429 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.71

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: rs6671760; hg19: chr1-57140665; COSMIC: COSV64802925;