rs2302531

Positions:

• chr7-151570267-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016203.4(PRKAG2):​c.1052-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,577,214 control chromosomes in the GnomAD database, including 13,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1123 hom., cov: 33)
  • Exomes 𝑓: 0.12 (12219 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.757

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-151570267-G-A is Benign according to our data. Variant chr7-151570267-G-A is described in ClinVar as [Benign]. Clinvar id is 260694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.1052-42C>T		intron_variant		ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.1052-42C>T		intron_variant		1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16061 AN: 152046 Hom.: 1119 Cov.: 33

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.148 AC: 36287 AN: 245054 Hom.: 3308 AF XY: 0.149 AC XY: 19787 AN XY: 132714

Gnomad AFR exome AF: 0.0287

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.122 AC: 173407 AN: 1425050 Hom.: 12219 Cov.: 29 AF XY: 0.125 AC XY: 88296 AN XY: 708664

Gnomad4 AFR exome AF: 0.0271

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.106 AC: 16063 AN: 152164 Hom.: 1123 Cov.: 33 AF XY: 0.109 AC XY: 8113 AN XY: 74374

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.126

Alfa AF: 0.120 Hom.: 281

Bravo AF: 0.106

Asia WGS AF: 0.252 AC: 878 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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	-0.75
CADD	Benign	12
DANN	Benign	0.64

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: rs2302531; hg19: chr7-151267353; COSMIC: COSV55221795; COSMIC: COSV55221795;