rs7801616

chr7-151755542-T-C

Variant summary

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

The NM_016203.4(PRKAG2):c.466+25610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,824 control chromosomes in the GnomAD database, including 27,842 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 0.60 (27842 hom., cov: 30)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.466+25610A>G		intron_variant		ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.466+25610A>G		intron_variant		1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90456 AN: 151706 Hom.: 27795 Cov.: 30

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.596 AC: 90561 AN: 151824 Hom.: 27842 Cov.: 30 AF XY: 0.600 AC XY: 44497 AN XY: 74182

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.616

Alfa AF: 0.576 Hom.: 36560

Bravo AF: 0.613

Asia WGS AF: 0.889 AC: 3084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.7
Dann	Benign	0.61

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: rs7801616; hg19: chr7-151452628;