Variant rs75750979 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.114+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,561,556 control chromosomes in the GnomAD database, including 2,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 258 hom., cov: 31)

Exomes 𝑓: 0.047 ( 2229 hom. )

Consequence

PRKAG2
NM_016203.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.762

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:

PRKAG2 (HGNC:):

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=-0.75).

BP6

Variant 7-151876464-G-A is Benign according to our data. Variant chr7-151876464-G-A is described in ClinVar as [Benign]. Clinvar id is 260695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-151876464-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 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.114+43C>T		intron_variant		ENST00000287878.9	NP_057287.2	Q9UGJ0-1A0A090N8Q6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9 linkuse as main transcript	c.114+43C>T		intron_variant		1	NM_016203.4	ENSP00000287878.3		Q9UGJ0-1

Frequencies

GnomAD3 genomes

AF:

0.0426

AC:

6484

AN:

152138

Hom.:

258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0426

Gnomad OTH

AF:

0.0531

GnomAD3 exomes

AF:

0.0626

AC:

14987

AN:

239284

Hom.:

856

AF XY:

0.0569

AC XY:

7433

AN XY:

130672

show subpopulations

Gnomad AFR exome

AF:

0.00895

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0443

Gnomad OTH exome

AF:

0.0641

GnomAD4 exome

AF:

0.0467

AC:

65822

AN:

1409300

Hom.:

2229

Cov.:

AF XY:

0.0455

AC XY:

32032

AN XY:

704028

show subpopulations

Gnomad4 AFR exome

AF:

0.00839

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.0296

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.0428

Gnomad4 OTH exome

AF:

0.0493

GnomAD4 genome

AF:

0.0426

AC:

6485

AN:

152256

Hom.:

258

Cov.:

AF XY:

0.0434

AC XY:

3230

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.0218

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.0426

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0384

Hom.:

Bravo

AF:

0.0507

Asia WGS

AF:

0.106

AC:

368

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.8

DANN

Benign

0.94

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