rs1860746

Variant names:

• chr7-151688267-C-A
• rs1860746
• NM_016203.4:c.467-12630G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016203.4(PRKAG2):​c.467-12630G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,148 control chromosomes in the GnomAD database, including 2,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2252 hom., cov: 32)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.576
• Publications: 4 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

ENSG00000299629 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-151688267-C-A is Benign according to our data. Variant chr7-151688267-C-A is described in ClinVar as Benign. ClinVar VariationId is 1164564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.467-12630G>T		intron_variant	Intron 3 of 15	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.467-12630G>T		intron_variant	Intron 3 of 15	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25632 AN: 152030 Hom.: 2248 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00637

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.169 AC: 25651 AN: 152148 Hom.: 2252 Cov.: 32 AF XY: 0.165 AC XY: 12247 AN XY: 74378

African (AFR) AF: 0.194 AC: 8065 AN: 41514

American (AMR) AF: 0.138 AC: 2106 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3468

East Asian (EAS) AF: 0.00619 AC: 32 AN: 5168

South Asian (SAS) AF: 0.0780 AC: 376 AN: 4820

European-Finnish (FIN) AF: 0.169 AC: 1796 AN: 10598

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12112 AN: 67968

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.172 Hom.: 3326

Bravo AF: 0.167

Asia WGS AF: 0.0610 AC: 216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lethal congenital glycogen storage disease of heart Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.33
PhyloP100		-0.58
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: rs1860746; hg19: chr7-151385353;