rs28938173

Variant names:

• chr7-151568750-G-C
• NM_016203.4:c.1199C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-151568750-G-C
• chr7-151568750-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016203.4(PRKAG2):​c.1199C>G​(p.Thr400Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRKAG2 NM_016203.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.74

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.1199C>G	p.Thr400Ser	missense_variant	Exon 11 of 16	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.1199C>G	p.Thr400Ser	missense_variant	Exon 11 of 16	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
CardioboostCm	Uncertain	0.59
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D;.;.;.;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;.
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Pathogenic	3.1	M;.;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.8	D;D;D;D;D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.011	D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		0.94	P;.;.;.;.
Vest4		0.88
MutPred		0.83		Gain of sheet (P = 0.1451);.;.;.;.;
MVP		0.98
MPC		1.5
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.58
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-151265836; COSMIC: COSV99836458; COSMIC: COSV99836458;