Variant 7-151595309-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: -3.41

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
PRKAG2	NM_016203.4 linkuse as main transcript	c.864+35_864+36insA		intron_variant		ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9 linkuse as main transcript	c.864+35_864+36insA		intron_variant		1	NM_016203.4	P3	Q9UGJ0-1

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

GnomAD3 exomes

AF:

0.764

AC:

186641

AN:

244310

Hom.:

71962

AF XY:

0.768

AC XY:

101613

AN XY:

132360

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 SAS exome

AF:

0.832

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

Gnomad4 AFR exome

AF:

0.669

Gnomad4 AMR exome

AF:

0.739

Gnomad4 ASJ exome

AF:

0.740

Gnomad4 EAS exome

AF:

0.986

Gnomad4 SAS exome

AF:

0.830

Gnomad4 FIN exome

AF:

0.783

Gnomad4 NFE exome

AF:

0.733

Gnomad4 OTH exome

AF:

0.755

GnomAD4 genome

AF:

0.729

AC:

110756

AN:

152000

Hom.:

40657

Cov.:

AF XY:

0.734

AC XY:

54562

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.669

Gnomad4 AMR

AF:

0.733

Gnomad4 ASJ

AF:

0.733

Gnomad4 EAS

AF:

0.984

Gnomad4 SAS

AF:

0.844

Gnomad4 FIN

AF:

0.775

Gnomad4 NFE

AF:

0.731

Gnomad4 OTH

AF:

0.750

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wolff-Parkinson-White pattern

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Hypertrophic cardiomyopathy 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Lethal congenital glycogen storage disease of heart

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over