chr7-151849504-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016203.4(PRKAG2):​c.114+27003A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,070 control chromosomes in the GnomAD database, including 22,550 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 ( 22550 hom., cov: 33)

Consequence

PRKAG2
NM_016203.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.603

Publications

16 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKAG2NM_016203.4 linkc.114+27003A>G intron_variant Intron 1 of 15 ENST00000287878.9 NP_057287.2 Q9UGJ0-1A0A090N8Q6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKAG2ENST00000287878.9 linkc.114+27003A>G intron_variant Intron 1 of 15 1 NM_016203.4 ENSP00000287878.3 Q9UGJ0-1

Frequencies

GnomAD3 genomes
AF:
0.536
AC:
81427
AN:
151952
Hom.:
22526
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.642
Gnomad AMI
AF:
0.538
Gnomad AMR
AF:
0.580
Gnomad ASJ
AF:
0.456
Gnomad EAS
AF:
0.723
Gnomad SAS
AF:
0.370
Gnomad FIN
AF:
0.461
Gnomad MID
AF:
0.617
Gnomad NFE
AF:
0.473
Gnomad OTH
AF:
0.558
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.536
AC:
81500
AN:
152070
Hom.:
22550
Cov.:
33
AF XY:
0.533
AC XY:
39609
AN XY:
74366
show subpopulations
African (AFR)
AF:
0.642
AC:
26629
AN:
41446
American (AMR)
AF:
0.580
AC:
8871
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.456
AC:
1583
AN:
3472
East Asian (EAS)
AF:
0.722
AC:
3734
AN:
5172
South Asian (SAS)
AF:
0.369
AC:
1778
AN:
4818
European-Finnish (FIN)
AF:
0.461
AC:
4881
AN:
10580
Middle Eastern (MID)
AF:
0.602
AC:
177
AN:
294
European-Non Finnish (NFE)
AF:
0.473
AC:
32179
AN:
67982
Other (OTH)
AF:
0.560
AC:
1182
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1903
3805
5708
7610
9513
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
692
1384
2076
2768
3460
<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:
0.499
Hom.:
81214
Bravo
AF:
0.562
Asia WGS
AF:
0.595
AC:
2065
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.60
DANN
Benign
0.20
PhyloP100
-0.60
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs7795096; hg19: chr7-151546589; API