rs2727537

Variant names:

• chr7-151675960-G-A
• rs2727537
• NM_016203.4:c.467-323C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151675960-G-A
• chr7-151675960-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016203.4(PRKAG2):​c.467-323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,858 control chromosomes in the GnomAD database, including 24,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (24536 hom., cov: 30)
• Consequence: PRKAG2 NM_016203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.87
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-151675960-G-A is Benign according to our data. Variant chr7-151675960-G-A is described in ClinVar as Benign. ClinVar VariationId is 1252196.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.467-323C>T		intron_variant	Intron 3 of 15	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.467-323C>T		intron_variant	Intron 3 of 15	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84895 AN: 151740 Hom.: 24533 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 84925 AN: 151858 Hom.: 24536 Cov.: 30 AF XY: 0.557 AC XY: 41336 AN XY: 74188

African (AFR) AF: 0.419 AC: 17336 AN: 41404

American (AMR) AF: 0.601 AC: 9171 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2288 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2036 AN: 5136

South Asian (SAS) AF: 0.626 AC: 3009 AN: 4804

European-Finnish (FIN) AF: 0.567 AC: 5966 AN: 10530

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43014 AN: 67954

Other (OTH) AF: 0.569 AC: 1201 AN: 2112

Alfa AF: 0.530 Hom.: 7774

Bravo AF: 0.554

Asia WGS AF: 0.493 AC: 1714 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.89
PhyloP100		-1.9
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: rs2727537; hg19: chr7-151373046;