rs9648724

chr7-151805216-G-Achr7-151805216-G-T

Variant summary

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

The NM_016203.4(PRKAG2):c.115-18675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,036 control chromosomes in the GnomAD database, including 3,529 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 (3529 hom., cov: 32)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.115-18675C>T		intron_variant		ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.115-18675C>T		intron_variant		1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31804 AN: 151918 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.209 AC: 31820 AN: 152036 Hom.: 3529 Cov.: 32 AF XY: 0.209 AC XY: 15530 AN XY: 74312

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.222

Alfa AF: 0.222 Hom.: 6657

Bravo AF: 0.200

Asia WGS AF: 0.258 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.4
Dann	Benign	0.72

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: rs9648724; hg19: chr7-151502302;