rs7805747

chr7-151710715-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016203.4(PRKAG2):c.467-35078C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,088 control chromosomes in the GnomAD database, including 5,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5497 hom., cov: 32)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.320

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 7-151710715-G-A is Benign according to our data. Variant chr7-151710715-G-A is described in ClinVar as [Benign]. Clinvar id is 1227412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.467-35078C>T		intron_variant		ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.467-35078C>T		intron_variant		1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39295 AN: 151970 Hom.: 5490 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.259 AC: 39334 AN: 152088 Hom.: 5497 Cov.: 32 AF XY: 0.247 AC XY: 18394 AN XY: 74330

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0788

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.258

Alfa AF: 0.266 Hom.: 8695

Bravo AF: 0.265

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 02, 2020

This variant is associated with the following publications: (PMID: 30559760) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.54
Dann	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs7805747; hg19: chr7-151407801;