rs77902041

Variant names:

• chr7-151876495-G-A
• rs77902041
• NM_016203.4:c.114+12C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016203.4(PRKAG2):​c.114+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 1,601,166 control chromosomes in the GnomAD database, including 3,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (263 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3689 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.395
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 7-151876495-G-A is Benign according to our data. Variant chr7-151876495-G-A is described in ClinVar as Benign. ClinVar VariationId is 45689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0743 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	NM_016203.4	MANE Select	c.114+12C>T		intron	N/A	NP_057287.2
	PRKAG2	NM_001407021.1		c.114+12C>T		intron	N/A	NP_001393950.1
	PRKAG2	NM_001407022.1		c.114+12C>T		intron	N/A	NP_001393951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.114+12C>T		intron	N/A	ENSP00000287878.3	Q9UGJ0-1
	PRKAG2	ENST00000488258.5	TSL:1	n.114+12C>T		intron	N/A	ENSP00000420783.1	F8WDA1
	PRKAG2	ENST00000652321.2		c.114+12C>T		intron	N/A	ENSP00000498886.2	A0A494C155

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7416 AN: 152146 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0469

GnomAD2 exomes AF: 0.0509 AC: 12390 AN: 243254 AF XY: 0.0523

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0324

Gnomad ASJ exome AF: 0.0651

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0530

Gnomad NFE exome AF: 0.0736

Gnomad OTH exome AF: 0.0610

GnomAD4 exome AF: 0.0687 AC: 99576 AN: 1448904 Hom.: 3689 Cov.: 31 AF XY: 0.0677 AC XY: 48837 AN XY: 721456

African (AFR) AF: 0.0108 AC: 361 AN: 33388

American (AMR) AF: 0.0354 AC: 1584 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0650 AC: 1698 AN: 26104

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39668

South Asian (SAS) AF: 0.0333 AC: 2867 AN: 86148

European-Finnish (FIN) AF: 0.0570 AC: 2526 AN: 44340

Middle Eastern (MID) AF: 0.0514 AC: 285 AN: 5548

European-Non Finnish (NFE) AF: 0.0779 AC: 86419 AN: 1108828

Other (OTH) AF: 0.0637 AC: 3831 AN: 60160

GnomAD4 genome AF: 0.0487 AC: 7418 AN: 152262 Hom.: 263 Cov.: 32 AF XY: 0.0465 AC XY: 3460 AN XY: 74456

African (AFR) AF: 0.0132 AC: 550 AN: 41560

American (AMR) AF: 0.0333 AC: 510 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3466

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4828

European-Finnish (FIN) AF: 0.0515 AC: 546 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0760 AC: 5171 AN: 68010

Other (OTH) AF: 0.0459 AC: 97 AN: 2112

Alfa AF: 0.0527 Hom.: 122

Bravo AF: 0.0466

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Hypertrophic cardiomyopathy (1)
-	-	1	Hypertrophic cardiomyopathy 6 (1)
-	-	1	Lethal congenital glycogen storage disease of heart (1)
-	-	1	Wolff-Parkinson-White pattern (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs77902041; hg19: chr7-151573580;