rs1051956

Variant names:

• chr7-151556679-C-A
• rs1051956
• NM_016203.4:c.*522G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151556679-C-A
• chr7-151556679-C-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.*522G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 155,478 control chromosomes in the GnomAD database, including 25,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (24409 hom., cov: 34)
  • Exomes 𝑓: 0.59 (597 hom.)
• Consequence: PRKAG2 NM_016203.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.573
• Publications: 10 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 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, 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: Genomics England PanelApp
• Wolff-Parkinson-White syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-151556679-C-A is Benign according to our data. Variant chr7-151556679-C-A is described in ClinVar as Benign. ClinVar VariationId is 359335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 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.*522G>T		3_prime_UTR	Exon 16 of 16	NP_057287.2
	PRKAG2	NM_001407021.1		c.*3663G>T		3_prime_UTR	Exon 15 of 15	NP_001393950.1
	PRKAG2	NM_001407022.1		c.*3663G>T		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.*522G>T		3_prime_UTR	Exon 16 of 16	ENSP00000287878.3	Q9UGJ0-1
	PRKAG2	ENST00000418337.6	TSL:1	c.*522G>T		3_prime_UTR	Exon 12 of 12	ENSP00000387386.2	Q9UGJ0-2
	PRKAG2	ENST00000652321.2		c.*522G>T		3_prime_UTR	Exon 16 of 16	ENSP00000498886.2	A0A494C155

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82803 AN: 152028 Hom.: 24397 Cov.: 34

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.587 AC: 1955 AN: 3332 Hom.: 597 Cov.: 0 AF XY: 0.598 AC XY: 1040 AN XY: 1740

African (AFR) AF: 0.250 AC: 3 AN: 12

American (AMR) AF: 0.471 AC: 370 AN: 786

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 16 AN: 20

East Asian (EAS) AF: 0.721 AC: 62 AN: 86

South Asian (SAS) AF: 0.590 AC: 229 AN: 388

European-Finnish (FIN) AF: 0.688 AC: 11 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.624 AC: 1204 AN: 1928

Other (OTH) AF: 0.625 AC: 60 AN: 96

GnomAD4 genome AF: 0.544 AC: 82837 AN: 152146 Hom.: 24409 Cov.: 34 AF XY: 0.551 AC XY: 40967 AN XY: 74378

African (AFR) AF: 0.298 AC: 12363 AN: 41500

American (AMR) AF: 0.553 AC: 8450 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2308 AN: 3468

East Asian (EAS) AF: 0.714 AC: 3691 AN: 5172

South Asian (SAS) AF: 0.633 AC: 3056 AN: 4828

European-Finnish (FIN) AF: 0.692 AC: 7323 AN: 10586

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43890 AN: 67998

Other (OTH) AF: 0.570 AC: 1201 AN: 2108

Alfa AF: 0.608 Hom.: 36146

Bravo AF: 0.522

Asia WGS AF: 0.631 AC: 2194 AN: 3478

ClinVar

ClinVar submissions

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	-0.94
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.57
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: rs1051956; hg19: chr7-151253765;