7-151556679-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016203.4(PRKAG2):c.*522G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 155,478 control chromosomes in the GnomAD database, including 25,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 24409 hom., cov: 34)

Exomes 𝑓: 0.59 ( 597 hom. )

Consequence

PRKAG2
NM_016203.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.573

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 7-151556679-C-A is Benign according to our data. Variant chr7-151556679-C-A is described in ClinVar as [Benign]. Clinvar id is 359335.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/exons	MANE	UniProt
PRKAG2	NM_016203.4 linkuse as main transcript	c.*522G>T		3_prime_UTR_variant	16/16	ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9 linkuse as main transcript	c.*522G>T		3_prime_UTR_variant	16/16	1	NM_016203.4	P3	Q9UGJ0-1

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82803

AN:

152028

Hom.:

24397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.666

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.632

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.565

GnomAD4 exome

AF:

0.587

AC:

1955

AN:

3332

Hom.:

597

Cov.:

AF XY:

0.598

AC XY:

1040

AN XY:

1740

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.800

Gnomad4 EAS exome

AF:

0.721

Gnomad4 SAS exome

AF:

0.590

Gnomad4 FIN exome

AF:

0.688

Gnomad4 NFE exome

AF:

0.624

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.544

AC:

82837

AN:

152146

Hom.:

24409

Cov.:

AF XY:

0.551

AC XY:

40967

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.553

Gnomad4 ASJ

AF:

0.666

Gnomad4 EAS

AF:

0.714

Gnomad4 SAS

AF:

0.633

Gnomad4 FIN

AF:

0.692

Gnomad4 NFE

AF:

0.645

Gnomad4 OTH

AF:

0.570

Alfa

AF:

0.623

Hom.:

29026

Bravo

AF:

0.522

Asia WGS

AF:

0.631

AC:

2194

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wolff-Parkinson-White pattern

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hypertrophic cardiomyopathy 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

Cadd

Benign

3.1

Dann

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over