7-151876355-G-C

Variant names:

• chr7-151876355-G-C
• rs181719939
• NM_016203.4:c.114+152C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016203.4(PRKAG2):​c.114+152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 742,958 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (9 hom., cov: 31)
  • Exomes 𝑓: 0.00089 (3 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.192
• Publications: 0 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-AS1 (HGNC:40468): (PRKAG2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-151876355-G-C is Benign according to our data. Variant chr7-151876355-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1190823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00569 (866/152144) while in subpopulation AFR AF = 0.0191 (792/41536). AF 95% confidence interval is 0.018. There are 9 homozygotes in GnomAd4. There are 415 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 866 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.114+152C>G		intron_variant	Intron 1 of 15	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.114+152C>G		intron_variant	Intron 1 of 15	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes AF: 0.00568 AC: 864 AN: 152026 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.000885 AC: 523 AN: 590814 Hom.: 3 AF XY: 0.000785 AC XY: 246 AN XY: 313224

African (AFR) AF: 0.0176 AC: 276 AN: 15660

American (AMR) AF: 0.00231 AC: 67 AN: 29052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17132

East Asian (EAS) AF: 0.00 AC: 0 AN: 32412

South Asian (SAS) AF: 0.0000678 AC: 4 AN: 58958

European-Finnish (FIN) AF: 0.0000312 AC: 1 AN: 32066

Middle Eastern (MID) AF: 0.00385 AC: 9 AN: 2338

European-Non Finnish (NFE) AF: 0.000285 AC: 106 AN: 372336

Other (OTH) AF: 0.00194 AC: 60 AN: 30860

GnomAD4 genome AF: 0.00569 AC: 866 AN: 152144 Hom.: 9 Cov.: 31 AF XY: 0.00558 AC XY: 415 AN XY: 74374

African (AFR) AF: 0.0191 AC: 792 AN: 41536

American (AMR) AF: 0.00248 AC: 38 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67988

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00409 Hom.: 0

Bravo AF: 0.00646

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 06, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism

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: rs181719939; hg19: chr7-151573440;