rs1001117

Positions:

• chr7-151744884-G-A

Variant summary

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

The NM_016203.4(PRKAG2):​c.466+36268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,088 control chromosomes in the GnomAD database, including 7,939 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 0.32 (7939 hom., cov: 32)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.466+36268C>T		intron_variant		ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.466+36268C>T		intron_variant		1	NM_016203.4	ENSP00000287878	P3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48789 AN: 151970 Hom.: 7930 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.321 AC: 48823 AN: 152088 Hom.: 7939 Cov.: 32 AF XY: 0.318 AC XY: 23677 AN XY: 74344

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.317

Alfa AF: 0.325 Hom.: 4581

Bravo AF: 0.320

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.34

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: rs1001117; hg19: chr7-151441970;