7-151556179-CAAA-CAAAA

Variant names:

• chr7-151556179-C-CA
• rs11329945
• NM_016203.4:c.*1021dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_016203.4(PRKAG2):​c.*1021dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (398 hom., cov: 0)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: PRKAG2 NM_016203.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 2 publications found

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]

PRKAG2 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• PRKAG2-related cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• lethal congenital glycogen storage disease of heart

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
• Wolff-Parkinson-White syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.*1021dupT		3_prime_UTR_variant	Exon 16 of 16	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.*1021dupT		3_prime_UTR_variant	Exon 16 of 16	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7089 AN: 143458 Hom.: 395 Cov.: 0

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000401

Gnomad SAS AF: 0.00300

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.00993

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.0196 AC: 2 AN: 102 Hom.: 0 Cov.: 0 AF XY: 0.0263 AC XY: 2 AN XY: 76

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0196 AC: 2 AN: 102

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0495 AC: 7099 AN: 143474 Hom.: 398 Cov.: 0 AF XY: 0.0494 AC XY: 3437 AN XY: 69594

African (AFR) AF: 0.145 AC: 5657 AN: 38898

American (AMR) AF: 0.0287 AC: 418 AN: 14560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.000402 AC: 2 AN: 4976

South Asian (SAS) AF: 0.00259 AC: 12 AN: 4640

European-Finnish (FIN) AF: 0.0185 AC: 145 AN: 7848

Middle Eastern (MID) AF: 0.0108 AC: 3 AN: 278

European-Non Finnish (NFE) AF: 0.0119 AC: 783 AN: 66014

Other (OTH) AF: 0.0401 AC: 79 AN: 1972

Alfa AF: 0.00787 Hom.: 848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11329945; hg19: chr7-151253265;