7-151556140-C-T

Position:

• chr7-151556140-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_016203.4(PRKAG2):​c.*1061G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 146,038 control chromosomes in the GnomAD database, including 23,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23702 hom., cov: 26)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: PRKAG2 NM_016203.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.91

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 Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 7-151556140-C-T is Benign according to our data. Variant chr7-151556140-C-T is described in ClinVar as [Benign]. Clinvar id is 359320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG2	NM_016203.4	c.*1061G>A		3_prime_UTR_variant	16/16	ENST00000287878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG2	ENST00000287878.9	c.*1061G>A		3_prime_UTR_variant	16/16	1	NM_016203.4	P3

Frequencies

GnomAD3 genomes AF: 0.551 AC: 80417 AN: 145990 Hom.: 23701 Cov.: 26

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.581

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 0.375

GnomAD4 genome AF: 0.551 AC: 80415 AN: 146030 Hom.: 23702 Cov.: 26 AF XY: 0.557 AC XY: 39514 AN XY: 70944

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.581

Alfa AF: 0.600 Hom.: 5608

Bravo AF: 0.528

Asia WGS AF: 0.627 AC: 2160 AN: 3444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wolff-Parkinson-White pattern Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Hypertrophic cardiomyopathy 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.89

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

Other links and lift over

dbSNP: rs7429; hg19: chr7-151253226;