NM_016203.4:c.*1021delT

Variant names:

• chr7-151556179-CA-C
• rs11329945
• NM_016203.4:c.*1021delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016203.4(PRKAG2):​c.*1021delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (22755 hom., cov: 0)
  • Exomes 𝑓: 0.69 (23 hom.)
• Consequence: PRKAG2 NM_016203.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 1.01
• Publications: 2 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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• PRKAG2-related cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• lethal congenital glycogen storage disease of heart

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
• Wolff-Parkinson-White syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-151556179-CA-C is Benign according to our data. Variant chr7-151556179-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 359326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.*1021delT		3_prime_UTR_variant	Exon 16 of 16	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.*1021delT		3_prime_UTR_variant	Exon 16 of 16	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 78321 AN: 143406 Hom.: 22754 Cov.: 0

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.686 AC: 70 AN: 102 Hom.: 23 Cov.: 0 AF XY: 0.658 AC XY: 50 AN XY: 76

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.686 AC: 70 AN: 102

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.546 AC: 78317 AN: 143422 Hom.: 22755 Cov.: 0 AF XY: 0.552 AC XY: 38377 AN XY: 69554

African (AFR) AF: 0.300 AC: 11653 AN: 38898

American (AMR) AF: 0.557 AC: 8103 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2259 AN: 3396

East Asian (EAS) AF: 0.713 AC: 3549 AN: 4976

South Asian (SAS) AF: 0.638 AC: 2957 AN: 4632

European-Finnish (FIN) AF: 0.686 AC: 5376 AN: 7840

Middle Eastern (MID) AF: 0.601 AC: 167 AN: 278

European-Non Finnish (NFE) AF: 0.648 AC: 42740 AN: 65994

Other (OTH) AF: 0.577 AC: 1135 AN: 1966

Alfa AF: 0.369 Hom.: 848

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Wolff-Parkinson-White pattern Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lethal congenital glycogen storage disease of heart Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
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: rs11329945; hg19: chr7-151253265; COSMIC: COSV55224745; COSMIC: COSV55224745;