rs5017427

Variant names:

• chr7-151558117-A-G
• rs5017427
• NM_016203.4:c.1679-885T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-151558117-A-G
• chr7-151558117-A-T

Variant summary

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

The NM_016203.4(PRKAG2):​c.1679-885T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 984,784 control chromosomes in the GnomAD database, including 200,901 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 0.54 (24155 hom., cov: 32)
  • Exomes 𝑓: 0.65 (176746 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	NM_016203.4	MANE Select	c.1679-885T>C		intron	N/A	NP_057287.2
	PRKAG2	NM_001407021.1		c.*2225T>C		3_prime_UTR	Exon 15 of 15	NP_001393950.1
	PRKAG2	NM_001407022.1		c.*2225T>C		3_prime_UTR	Exon 15 of 15	NP_001393951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.1679-885T>C		intron	N/A	ENSP00000287878.3
	PRKAG2	ENST00000392801.6	TSL:1	c.1547-885T>C		intron	N/A	ENSP00000376549.2
	PRKAG2	ENST00000418337.6	TSL:1	c.956-885T>C		intron	N/A	ENSP00000387386.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81743 AN: 151916 Hom.: 24142 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.649 AC: 540223 AN: 832750 Hom.: 176746 Cov.: 39 AF XY: 0.648 AC XY: 249351 AN XY: 384550

African (AFR) AF: 0.230 AC: 3629 AN: 15782

American (AMR) AF: 0.555 AC: 546 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 3381 AN: 5152

East Asian (EAS) AF: 0.716 AC: 2595 AN: 3626

South Asian (SAS) AF: 0.642 AC: 10567 AN: 16454

European-Finnish (FIN) AF: 0.699 AC: 193 AN: 276

Middle Eastern (MID) AF: 0.603 AC: 975 AN: 1618

European-Non Finnish (NFE) AF: 0.658 AC: 500936 AN: 761572

Other (OTH) AF: 0.638 AC: 17401 AN: 27286

GnomAD4 genome AF: 0.538 AC: 81775 AN: 152034 Hom.: 24155 Cov.: 32 AF XY: 0.545 AC XY: 40464 AN XY: 74308

African (AFR) AF: 0.272 AC: 11291 AN: 41458

American (AMR) AF: 0.552 AC: 8443 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2279 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3671 AN: 5142

South Asian (SAS) AF: 0.632 AC: 3048 AN: 4820

European-Finnish (FIN) AF: 0.692 AC: 7311 AN: 10568

Middle Eastern (MID) AF: 0.566 AC: 163 AN: 288

European-Non Finnish (NFE) AF: 0.647 AC: 43987 AN: 67986

Other (OTH) AF: 0.567 AC: 1197 AN: 2112

Alfa AF: 0.572 Hom.: 3149

Bravo AF: 0.516

Asia WGS AF: 0.629 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.35
PhyloP100		-1.1
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: rs5017427; hg19: chr7-151255203;