dbSNP rs75750979: PRKAG2:c.114+43C>T (chr7-151876464-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

3 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 links:

PRKAG2-AS1 (HGNC:40468): (PRKAG2 antisense RNA 1)

PRKAG2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016203.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PRKAG2	NM_016203.4	MANE Select	c.114+43C>T	intron	N/A	NP_057287.2
PRKAG2	NM_001407021.1		c.114+43C>T	intron	N/A	NP_001393950.1
PRKAG2	NM_001407022.1		c.114+43C>T	intron	N/A	NP_001393951.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.114+43C>T	intron	N/A	ENSP00000287878.3	Q9UGJ0-1
PRKAG2	ENST00000488258.5	TSL:1	n.114+43C>T	intron	N/A	ENSP00000420783.1	F8WDA1
PRKAG2	ENST00000652321.2		c.114+43C>T	intron	N/A	ENSP00000498886.2	A0A494C155

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

GnomAD2 exomes

AF:

0.0626

AC:

14987

AN:

239284

AF XY:

0.0569

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 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

African (AFR)

AF:

0.00839

AC:

273

AN:

32542

American (AMR)

AF:

0.136

AC:

6076

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.0296

AC:

768

AN:

25908

East Asian (EAS)

AF:

0.181

AC:

7149

AN:

39494

South Asian (SAS)

AF:

0.0163

AC:

1392

AN:

85350

European-Finnish (FIN)

AF:

0.0256

AC:

1063

AN:

41498

Middle Eastern (MID)

AF:

0.0271

AC:

130

AN:

4790

European-Non Finnish (NFE)

AF:

0.0428

AC:

46071

AN:

1076304

Other (OTH)

AF:

0.0493

AC:

2900

AN:

58770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3382

6764

10147

13529

16911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1816

3632

5448

7264

9080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0426

AC:

6485

AN:

152256

Hom.:

258

Cov.:

AF XY:

0.0434

AC XY:

3230

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0115

AC:

478

AN:

41584

American (AMR)

AF:

0.102

AC:

1560

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

105

AN:

3472

East Asian (EAS)

AF:

0.190

AC:

973

AN:

5130

South Asian (SAS)

AF:

0.0218

AC:

105

AN:

4826

European-Finnish (FIN)

AF:

0.0228

AC:

242

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0426

AC:

2898

AN:

68008

Other (OTH)

AF:

0.0539

AC:

114

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

326

652

977

1303

1629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0384

Hom.:

Bravo

AF:

0.0507

Asia WGS

AF:

0.106

AC:

368

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.8

(source)

DANN

Benign

0.94

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over