rs181719939

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-151876355-G-A
• chr7-151876355-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016203.4(PRKAG2):​c.114+152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000339 in 590,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000339 AC: 2 AN: 590814 Hom.: 0 AF XY: 0.00000319 AC XY: 1 AN XY: 313226

African (AFR) AF: 0.00 AC: 0 AN: 15660

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 58958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2338

European-Non Finnish (NFE) AF: 0.00000537 AC: 2 AN: 372336

Other (OTH) AF: 0.00 AC: 0 AN: 30860

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.0
DANN	Benign	0.93
PhyloP100		-0.19

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;