Variant rs2302532 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016203.4(PRKAG2):c.1437+127T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 785,102 control chromosomes in the GnomAD database, including 26,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5026 hom., cov: 32)

Exomes 𝑓: 0.26 ( 21865 hom. )

Consequence

PRKAG2
NM_016203.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0200

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-151565219-A-C is Benign according to our data. Variant chr7-151565219-A-C is described in ClinVar as [Benign]. Clinvar id is 1221851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-151565219-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG2	NM_016203.4 linkuse as main transcript	c.1437+127T>G		intron_variant		ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9 linkuse as main transcript	c.1437+127T>G		intron_variant		1	NM_016203.4	ENSP00000287878	P3	Q9UGJ0-1

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38865

AN:

151992

Hom.:

5021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.281

GnomAD4 exome

AF:

0.259

AC:

164111

AN:

632992

Hom.:

21865

AF XY:

0.260

AC XY:

82896

AN XY:

319420

show subpopulations

Gnomad4 AFR exome

AF:

0.234

Gnomad4 AMR exome

AF:

0.321

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.256

AC:

38894

AN:

152110

Hom.:

5026

Cov.:

AF XY:

0.256

AC XY:

19019

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.277

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.263

Hom.:

816

Bravo

AF:

0.263

Asia WGS

AF:

0.308

AC:

1070

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.5

DANN

Benign

0.77

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