rs1881632

Variant names:

• chr7-151819255-G-A
• rs1881632
• NM_016203.4:c.115-32714C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151819255-G-A
• chr7-151819255-G-C
• chr7-151819255-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016203.4(PRKAG2):​c.115-32714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,244 control chromosomes in the GnomAD database, including 2,255 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2255 hom., cov: 33)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.115-32714C>T		intron_variant	Intron 1 of 15	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.115-32714C>T		intron_variant	Intron 1 of 15	1	NM_016203.4	ENSP00000287878.3
PRKAG2	ENST00000488258.5	n.115-32714C>T		intron_variant	Intron 1 of 9	1		ENSP00000420783.1
PRKAG2	ENST00000652321.2	c.115-32714C>T		intron_variant	Intron 1 of 15			ENSP00000498886.2
PRKAG2	ENST00000481434.5	n.620-32714C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24048 AN: 152126 Hom.: 2256 Cov.: 33

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24047 AN: 152244 Hom.: 2255 Cov.: 33 AF XY: 0.155 AC XY: 11564 AN XY: 74430

African (AFR) AF: 0.0757 AC: 3146 AN: 41554

American (AMR) AF: 0.167 AC: 2562 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5174

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4818

European-Finnish (FIN) AF: 0.144 AC: 1522 AN: 10604

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13884 AN: 68006

Other (OTH) AF: 0.149 AC: 316 AN: 2116

Alfa AF: 0.187 Hom.: 10764

Bravo AF: 0.150

Asia WGS AF: 0.156 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.82
PhyloP100		0.51
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: rs1881632; hg19: chr7-151516341; COSMIC: COSV55242569; COSMIC: COSV55242569;