rs2241053

chr7-151568628-C-T

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.1233+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,423,952 control chromosomes in the GnomAD database, including 64,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10734 hom., cov: 32)
  • Exomes 𝑓: 0.28 (53609 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.712

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=-0.85).
• BP6: Variant 7-151568628-C-T is Benign according to our data. Variant chr7-151568628-C-T is described in ClinVar as [Benign]. Clinvar id is 1244960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-151568628-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.1233+88G>A		intron_variant		ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.1233+88G>A		intron_variant		1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54057 AN: 151946 Hom.: 10698 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.281 AC: 357124 AN: 1271888 Hom.: 53609 AF XY: 0.280 AC XY: 178680 AN XY: 638608

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.356 AC: 54148 AN: 152064 Hom.: 10734 Cov.: 32 AF XY: 0.355 AC XY: 26370 AN XY: 74324

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.361

Alfa AF: 0.297 Hom.: 7050

Bravo AF: 0.377

Asia WGS AF: 0.413 AC: 1437 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	-0.85
Cadd	Benign	0.074
Dann	Benign	0.59

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: rs2241053; hg19: chr7-151265714; COSMIC: COSV55225467; COSMIC: COSV55225467;