NM_016203.4:c.864+35_864+36insA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_016203.4(PRKAG2):c.864+35_864+36insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,537,102 control chromosomes in the GnomAD database, including 430,414 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40657 hom., cov: 0)

Exomes 𝑓: 0.75 ( 389757 hom. )

Consequence

PRKAG2
NM_016203.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.41

Publications

5 publications found

Variant links:

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

PRKAG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 7-151595309-A-AT is Benign according to our data. Variant chr7-151595309-A-AT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4 link	c.864+35_864+36insA		intron_variant	Intron 6 of 15	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9 link	c.864+35_864+36insA		intron_variant	Intron 6 of 15	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110640

AN:

151882

Hom.:

40603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.733

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.843

Gnomad FIN

AF:

0.775

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.747

GnomAD2 exomes

AF:

0.764

AC:

186641

AN:

244310

AF XY:

0.768

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.739

Gnomad ASJ exome

AF:

0.736

Gnomad EAS exome

AF:

0.983

Gnomad FIN exome

AF:

0.786

Gnomad NFE exome

AF:

0.730

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.748

AC:

1035486

AN:

1385102

Hom.:

389757

Cov.:

AF XY:

0.750

AC XY:

519840

AN XY:

693320

show subpopulations

African (AFR)

AF:

0.669

AC:

21269

AN:

31790

American (AMR)

AF:

0.739

AC:

32733

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

18968

AN:

25618

East Asian (EAS)

AF:

0.986

AC:

38733

AN:

39294

South Asian (SAS)

AF:

0.830

AC:

70006

AN:

84350

European-Finnish (FIN)

AF:

0.783

AC:

40184

AN:

51334

Middle Eastern (MID)

AF:

0.713

AC:

4008

AN:

5620

European-Non Finnish (NFE)

AF:

0.733

AC:

765948

AN:

1044960

Other (OTH)

AF:

0.755

AC:

43637

AN:

57820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13168

26336

39503

52671

65839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18464

36928

55392

73856

92320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.729

AC:

110756

AN:

152000

Hom.:

40657

Cov.:

AF XY:

0.734

AC XY:

54562

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.669

AC:

27701

AN:

41418

American (AMR)

AF:

0.733

AC:

11202

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

2541

AN:

3468

East Asian (EAS)

AF:

0.984

AC:

5094

AN:

5178

South Asian (SAS)

AF:

0.844

AC:

4072

AN:

4824

European-Finnish (FIN)

AF:

0.775

AC:

8178

AN:

10548

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.731

AC:

49715

AN:

67978

Other (OTH)

AF:

0.750

AC:

1584

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1510

3020

4529

6039

7549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.686

Hom.:

4193

Bravo

AF:

0.717

Asia WGS

AF:

0.910

AC:

3165

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Wolff-Parkinson-White pattern

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hypertrophic cardiomyopathy 6

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Lethal congenital glycogen storage disease of heart

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-3.4

Mutation Taster

=28/72

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over