7-151556160-G-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016203.4(PRKAG2):c.*1040_*1041insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.54 (20896 hom., cov: 0)
  • Exomes 𝑓: 0.46 (0 hom.)
• Consequence: PRKAG2 NM_016203.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:9
• Conservation: PhyloP100: 0.882

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.*1040_*1041insT		3_prime_UTR_variant	16/16	ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.*1040_*1041insT		3_prime_UTR_variant	16/16	1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.538 AC: 73650 AN: 136902 Hom.: 20899 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.462 AC: 12 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 FIN exome AF: 0.462

GnomAD4 genome AF: 0.538 AC: 73638 AN: 136912 Hom.: 20896 Cov.: 0 AF XY: 0.543 AC XY: 35825 AN XY: 66006

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.556

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:9

Revision: criteria provided, single submitter

Submissions by phenotype

Wolff-Parkinson-White pattern Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Lethal congenital glycogen storage disease of heart Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56898021; hg19: chr7-151253246;