chr7-151556140-C-T

Variant names:

• chr7-151556140-C-T
• rs7429
• NM_016203.4:c.*1061G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001407021.1(PRKAG2):​c.*4202G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 146,038 control chromosomes in the GnomAD database, including 23,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23702 hom., cov: 26)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: PRKAG2 NM_001407021.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.91
• Publications: 9 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 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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 7-151556140-C-T is Benign according to our data. Variant chr7-151556140-C-T is described in ClinVar as Benign. ClinVar VariationId is 359320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407021.1. 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.*1061G>A		3_prime_UTR	Exon 16 of 16	NP_057287.2
	PRKAG2	NM_001407021.1		c.*4202G>A		3_prime_UTR	Exon 15 of 15	NP_001393950.1
	PRKAG2	NM_001407022.1		c.*4202G>A		3_prime_UTR	Exon 15 of 15	NP_001393951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.*1061G>A		3_prime_UTR	Exon 16 of 16	ENSP00000287878.3
	PRKAG2	ENST00000418337.6	TSL:1	c.*1061G>A		3_prime_UTR	Exon 12 of 12	ENSP00000387386.2
	PRKAG2	ENST00000867883.1		c.*1061G>A		3_prime_UTR	Exon 16 of 16	ENSP00000537942.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 80417 AN: 145990 Hom.: 23701 Cov.: 26

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.581

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.375 AC: 3 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.551 AC: 80415 AN: 146030 Hom.: 23702 Cov.: 26 AF XY: 0.557 AC XY: 39514 AN XY: 70944

African (AFR) AF: 0.315 AC: 12496 AN: 39672

American (AMR) AF: 0.559 AC: 8232 AN: 14738

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2305 AN: 3460

East Asian (EAS) AF: 0.716 AC: 3605 AN: 5034

South Asian (SAS) AF: 0.639 AC: 3015 AN: 4716

European-Finnish (FIN) AF: 0.688 AC: 5616 AN: 8164

Middle Eastern (MID) AF: 0.588 AC: 167 AN: 284

European-Non Finnish (NFE) AF: 0.648 AC: 43426 AN: 67052

Other (OTH) AF: 0.581 AC: 1170 AN: 2014

Alfa AF: 0.600 Hom.: 5608

Bravo AF: 0.528

Asia WGS AF: 0.627 AC: 2160 AN: 3444

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hypertrophic cardiomyopathy 6 (1)
-	-	1	not provided (1)
-	-	1	Wolff-Parkinson-White pattern (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		1.9
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: rs7429; hg19: chr7-151253226;