rs8961

Variant names:

• chr7-151557089-T-C
• rs8961
• NM_016203.4:c.*112A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-151557089-T-C
• chr7-151557089-T-A
• chr7-151557089-T-G

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.*112A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,515,240 control chromosomes in the GnomAD database, including 309,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24713 hom., cov: 32)
  • Exomes 𝑓: 0.64 (285247 hom.)
• Consequence: PRKAG2 NM_016203.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.139
• Publications: 21 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=-0.68).
• BP6: Variant 7-151557089-T-C is Benign according to our data. Variant chr7-151557089-T-C is described in ClinVar as Benign. ClinVar VariationId is 359342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 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.*112A>G		3_prime_UTR	Exon 16 of 16	NP_057287.2
	PRKAG2	NM_001407021.1		c.*3253A>G		3_prime_UTR	Exon 15 of 15	NP_001393950.1
	PRKAG2	NM_001407022.1		c.*3253A>G		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.*112A>G		3_prime_UTR	Exon 16 of 16	ENSP00000287878.3	Q9UGJ0-1
	PRKAG2	ENST00000392801.6	TSL:1	c.*112A>G		3_prime_UTR	Exon 16 of 16	ENSP00000376549.2	Q9UGJ0-3
	PRKAG2	ENST00000418337.6	TSL:1	c.*112A>G		3_prime_UTR	Exon 12 of 12	ENSP00000387386.2	Q9UGJ0-2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83568 AN: 151966 Hom.: 24700 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.643 AC: 876654 AN: 1363156 Hom.: 285247 Cov.: 20 AF XY: 0.644 AC XY: 439169 AN XY: 682248

African (AFR) AF: 0.295 AC: 9166 AN: 31112

American (AMR) AF: 0.520 AC: 22576 AN: 43454

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 16694 AN: 25306

East Asian (EAS) AF: 0.717 AC: 28005 AN: 39032

South Asian (SAS) AF: 0.638 AC: 53114 AN: 83230

European-Finnish (FIN) AF: 0.699 AC: 37046 AN: 52968

Middle Eastern (MID) AF: 0.612 AC: 3397 AN: 5554

European-Non Finnish (NFE) AF: 0.654 AC: 670419 AN: 1025466

Other (OTH) AF: 0.635 AC: 36237 AN: 57034

GnomAD4 genome AF: 0.550 AC: 83603 AN: 152084 Hom.: 24713 Cov.: 32 AF XY: 0.556 AC XY: 41358 AN XY: 74348

African (AFR) AF: 0.312 AC: 12958 AN: 41476

American (AMR) AF: 0.556 AC: 8500 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2311 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3699 AN: 5182

South Asian (SAS) AF: 0.635 AC: 3053 AN: 4810

European-Finnish (FIN) AF: 0.692 AC: 7318 AN: 10572

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43994 AN: 67978

Other (OTH) AF: 0.575 AC: 1213 AN: 2110

Alfa AF: 0.607 Hom.: 37946

Bravo AF: 0.529

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypertrophic cardiomyopathy 6 (1)
-	-	1	Wolff-Parkinson-White pattern (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.9
DANN	Benign	0.79
PhyloP100		0.14
Mutation Taster		=99/1	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: rs8961; hg19: chr7-151254175;