7-151556171-AC-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_016203.4(PRKAG2):​c.*1029delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 113,000 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 30)

Consequence

PRKAG2
NM_016203.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.358

Publications

0 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 -8 ACMG points.

BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000327 (37/113000) while in subpopulation AFR AF = 0.000836 (30/35872). AF 95% confidence interval is 0.000601. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
BS2
High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKAG2NM_016203.4 linkc.*1029delG 3_prime_UTR_variant Exon 16 of 16 ENST00000287878.9 NP_057287.2 Q9UGJ0-1A0A090N8Q6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKAG2ENST00000287878.9 linkc.*1029delG 3_prime_UTR_variant Exon 16 of 16 1 NM_016203.4 ENSP00000287878.3 Q9UGJ0-1

Frequencies

GnomAD3 genomes
AF:
0.000328
AC:
37
AN:
112922
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000839
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000538
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000673
GnomAD4 exome
Cov.:
0
GnomAD4 genome
AF:
0.000327
AC:
37
AN:
113000
Hom.:
0
Cov.:
30
AF XY:
0.000352
AC XY:
19
AN XY:
53914
show subpopulations
African (AFR)
AF:
0.000836
AC:
30
AN:
35872
American (AMR)
AF:
0.000538
AC:
6
AN:
11158
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2560
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3952
South Asian (SAS)
AF:
0.00
AC:
0
AN:
3124
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4930
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
222
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
48872
Other (OTH)
AF:
0.000671
AC:
1
AN:
1490
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1554444891; hg19: chr7-151253257; API