7-151556160-GA-G

Variant summary

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

The NM_016203.4(PRKAG2):c.*1040del 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 0.061 (697 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKAG2 NM_016203.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• 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 (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 8397 AN: 137000 Hom.: 693 Cov.: 0

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.00623

Gnomad EAS AF: 0.00526

Gnomad SAS AF: 0.00441

Gnomad FIN AF: 0.00199

Gnomad MID AF: 0.0146

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.0553

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0614 AC: 8411 AN: 137010 Hom.: 697 Cov.: 0 AF XY: 0.0601 AC XY: 3973 AN XY: 66054

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.00623

Gnomad4 EAS AF: 0.00528

Gnomad4 SAS AF: 0.00399

Gnomad4 FIN AF: 0.00199

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.0549

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

Submissions by phenotype

Wolff-Parkinson-White pattern Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Lethal congenital glycogen storage disease of heart Uncertain:1

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)		0.0		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: rs56898021; hg19: chr7-151253246;