rs2536082

Variant names:

• chr7-151694843-A-G
• rs2536082
• NM_016203.4:c.467-19206T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016203.4(PRKAG2):​c.467-19206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,260 control chromosomes in the GnomAD database, including 65,263 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 0.92 (65263 hom., cov: 32)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016203.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	NM_016203.4	MANE Select	c.467-19206T>C		intron	N/A	NP_057287.2
	PRKAG2	NM_001407021.1		c.467-19206T>C		intron	N/A	NP_001393950.1
	PRKAG2	NM_001407022.1		c.467-19206T>C		intron	N/A	NP_001393951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.467-19206T>C		intron	N/A	ENSP00000287878.3
	PRKAG2	ENST00000392801.6	TSL:1	c.335-19206T>C		intron	N/A	ENSP00000376549.2
	PRKAG2	ENST00000488258.5	TSL:1	n.467-19206T>C		intron	N/A	ENSP00000420783.1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140652 AN: 152142 Hom.: 65199 Cov.: 32

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.936

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

GnomAD4 genome AF: 0.925 AC: 140775 AN: 152260 Hom.: 65263 Cov.: 32 AF XY: 0.924 AC XY: 68762 AN XY: 74448

African (AFR) AF: 0.982 AC: 40791 AN: 41546

American (AMR) AF: 0.950 AC: 14542 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3030 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5162 AN: 5168

South Asian (SAS) AF: 0.940 AC: 4535 AN: 4824

European-Finnish (FIN) AF: 0.844 AC: 8946 AN: 10602

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60698 AN: 68022

Other (OTH) AF: 0.937 AC: 1983 AN: 2116

Alfa AF: 0.911 Hom.: 41668

Bravo AF: 0.935

Asia WGS AF: 0.979 AC: 3402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.42
PhyloP100		-0.79
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: rs2536082; hg19: chr7-151391929;