chr7-151708919-C-T

Variant names:

• chr7-151708919-C-T
• rs10480300
• NM_016203.4:c.467-33282G>A

Variant summary

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

The ENST00000287878.9(PRKAG2):​c.467-33282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,046 control chromosomes in the GnomAD database, including 4,620 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 0.24 (4620 hom., cov: 32)
• Consequence: PRKAG2 ENST00000287878.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 54 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000287878.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	NM_016203.4	MANE Select	c.467-33282G>A		intron	N/A	NP_057287.2
	PRKAG2	NM_001407021.1		c.467-33282G>A		intron	N/A	NP_001393950.1
	PRKAG2	NM_001407022.1		c.467-33282G>A		intron	N/A	NP_001393951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.467-33282G>A		intron	N/A	ENSP00000287878.3
	PRKAG2	ENST00000392801.6	TSL:1	c.335-33282G>A		intron	N/A	ENSP00000376549.2
	PRKAG2	ENST00000488258.5	TSL:1	n.467-33282G>A		intron	N/A	ENSP00000420783.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35937 AN: 151928 Hom.: 4615 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.237 AC: 35970 AN: 152046 Hom.: 4620 Cov.: 32 AF XY: 0.226 AC XY: 16815 AN XY: 74354

African (AFR) AF: 0.236 AC: 9762 AN: 41450

American (AMR) AF: 0.196 AC: 3001 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3466

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5178

South Asian (SAS) AF: 0.0767 AC: 369 AN: 4812

European-Finnish (FIN) AF: 0.181 AC: 1921 AN: 10600

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18904 AN: 67950

Other (OTH) AF: 0.242 AC: 508 AN: 2102

Alfa AF: 0.258 Hom.: 7615

Bravo AF: 0.239

Asia WGS AF: 0.0610 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.53
PhyloP100		-1.9
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: rs10480300; hg19: chr7-151406005;