NM_016203.4:c.114+43C>T

Variant names:

• chr7-151876464-G-A
• rs75750979
• NM_016203.4:c.114+43C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016203.4(PRKAG2):​c.114+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,561,556 control chromosomes in the GnomAD database, including 2,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (258 hom., cov: 31)
  • Exomes 𝑓: 0.047 (2229 hom.)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.762
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-151876464-G-A is Benign according to our data. Variant chr7-151876464-G-A is described in ClinVar as Benign. ClinVar VariationId is 260695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016203.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	NM_016203.4	MANE Select	c.114+43C>T		intron	N/A	NP_057287.2
	PRKAG2	NM_001407021.1		c.114+43C>T		intron	N/A	NP_001393950.1
	PRKAG2	NM_001407022.1		c.114+43C>T		intron	N/A	NP_001393951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.114+43C>T		intron	N/A	ENSP00000287878.3
	PRKAG2	ENST00000488258.5	TSL:1	n.114+43C>T		intron	N/A	ENSP00000420783.1
	PRKAG2-AS1	ENST00000765304.1		n.161G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6484 AN: 152138 Hom.: 258 Cov.: 31

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0531

GnomAD2 exomes AF: 0.0626 AC: 14987 AN: 239284 AF XY: 0.0569

Gnomad AFR exome AF: 0.00895

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.0275

Gnomad EAS exome AF: 0.198

Gnomad FIN exome AF: 0.0242

Gnomad NFE exome AF: 0.0443

Gnomad OTH exome AF: 0.0641

GnomAD4 exome AF: 0.0467 AC: 65822 AN: 1409300 Hom.: 2229 Cov.: 27 AF XY: 0.0455 AC XY: 32032 AN XY: 704028

African (AFR) AF: 0.00839 AC: 273 AN: 32542

American (AMR) AF: 0.136 AC: 6076 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.0296 AC: 768 AN: 25908

East Asian (EAS) AF: 0.181 AC: 7149 AN: 39494

South Asian (SAS) AF: 0.0163 AC: 1392 AN: 85350

European-Finnish (FIN) AF: 0.0256 AC: 1063 AN: 41498

Middle Eastern (MID) AF: 0.0271 AC: 130 AN: 4790

European-Non Finnish (NFE) AF: 0.0428 AC: 46071 AN: 1076304

Other (OTH) AF: 0.0493 AC: 2900 AN: 58770

GnomAD4 genome AF: 0.0426 AC: 6485 AN: 152256 Hom.: 258 Cov.: 31 AF XY: 0.0434 AC XY: 3230 AN XY: 74438

African (AFR) AF: 0.0115 AC: 478 AN: 41584

American (AMR) AF: 0.102 AC: 1560 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 105 AN: 3472

East Asian (EAS) AF: 0.190 AC: 973 AN: 5130

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4826

European-Finnish (FIN) AF: 0.0228 AC: 242 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0426 AC: 2898 AN: 68008

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0384 Hom.: 27

Bravo AF: 0.0507

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Benign	0.94
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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: rs75750979; hg19: chr7-151573549; COSMIC: COSV55225389; COSMIC: COSV55225389;