rs2727537

chr7-151675960-G-Achr7-151675960-G-C

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.467-323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,858 control chromosomes in the GnomAD database, including 24,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (24536 hom., cov: 30)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.87

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=-0.87).
• BP6: Variant 7-151675960-G-A is Benign according to our data. Variant chr7-151675960-G-A is described in ClinVar as [Benign]. Clinvar id is 1252196.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.467-323C>T		intron_variant		ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.467-323C>T		intron_variant		1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84895 AN: 151740 Hom.: 24533 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.559 AC: 84925 AN: 151858 Hom.: 24536 Cov.: 30 AF XY: 0.557 AC XY: 41336 AN XY: 74188

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.569

Alfa AF: 0.576 Hom.: 2858

Bravo AF: 0.554

Asia WGS AF: 0.493 AC: 1714 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

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.13
Dann	Benign	0.89

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: rs2727537; hg19: chr7-151373046;