rs1029947

Positions:

• chr7-151578666-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.865-2214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,072 control chromosomes in the GnomAD database, including 4,301 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 (4301 hom., cov: 32)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.865-2214A>G		intron_variant		ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.865-2214A>G		intron_variant		1	NM_016203.4	ENSP00000287878	P3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31979 AN: 151954 Hom.: 4269 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.211 AC: 32061 AN: 152072 Hom.: 4301 Cov.: 32 AF XY: 0.213 AC XY: 15849 AN XY: 74346

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.215

Alfa AF: 0.166 Hom.: 389

Bravo AF: 0.227

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.059
DANN	Benign	0.14

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: rs1029947; hg19: chr7-151275752;