rs5017427

Positions:

• chr7-151558117-A-G
• chr7-151558117-A-T

Variant summary

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

The NM_016203.4(PRKAG2):​c.1679-885T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 984,784 control chromosomes in the GnomAD database, including 200,901 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 (24155 hom., cov: 32)
  • Exomes 𝑓: 0.65 (176746 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

PRKAG2 (HGNC:9386): (protein kinase AMP-activated non-catalytic subunit gamma 2) AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family. Mutations in this gene have been associated with Wolff-Parkinson-White syndrome, familial hypertrophic cardiomyopathy, and glycogen storage disease of the heart. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2015]

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 (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.1679-885T>C		intron_variant		ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.1679-885T>C		intron_variant		1	NM_016203.4	ENSP00000287878	P3

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81743 AN: 151916 Hom.: 24142 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.649 AC: 540223 AN: 832750 Hom.: 176746 Cov.: 39 AF XY: 0.648 AC XY: 249351 AN XY: 384550

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.716

Gnomad4 SAS exome AF: 0.642

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.658

Gnomad4 OTH exome AF: 0.638

GnomAD4 genome AF: 0.538 AC: 81775 AN: 152034 Hom.: 24155 Cov.: 32 AF XY: 0.545 AC XY: 40464 AN XY: 74308

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.567

Alfa AF: 0.572 Hom.: 3149

Bravo AF: 0.516

Asia WGS AF: 0.629 AC: 2187 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	0.82
DANN	Benign	0.35

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: rs5017427; hg19: chr7-151255203;