NM_016203.4(PRKAG2):c.1114G>A (p.Asp372Asn) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 13, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003387879.1

Allele description [Variation Report for NM_016203.4(PRKAG2):c.1114G>A (p.Asp372Asn)]

NM_016203.4(PRKAG2):c.1114G>A (p.Asp372Asn)

Gene:

PRKAG2:protein kinase AMP-activated non-catalytic subunit gamma 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_016203.4(PRKAG2):c.1114G>A (p.Asp372Asn)

Other names:

p.Asp372Asn

HGVS:

NC_000007.14:g.151568835C>T
NG_007486.2:g.313397G>A
NM_001040633.2:c.982G>A
NM_001304527.2:c.739G>A
NM_001304531.2:c.391G>A
NM_001363698.2:c.742G>A
NM_016203.4:c.1114G>AMANE SELECT
NM_024429.2:c.391G>A
NP_001035723.1:p.Asp328Asn
NP_001291456.1:p.Asp247Asn
NP_001291460.1:p.Asp131Asn
NP_001350627.1:p.Asp248Asn
NP_057287.2:p.Asp372Asn
NP_077747.1:p.Asp131Asn
LRG_430t1:c.1114G>A
LRG_430:g.313397G>A
LRG_430p1:p.Asp372Asn
NC_000007.13:g.151265921C>T
NG_007486.1:g.313396G>A
NM_016203.3:c.1114G>A

Protein change:

D131N

Links:

dbSNP: rs760826751

NCBI 1000 Genomes Browser:

rs760826751

Molecular consequence:

NM_001040633.2:c.982G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304527.2:c.739G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304531.2:c.391G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363698.2:c.742G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024429.2:c.391G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Linear IgA Bullous Dermatosis
Linear IgA Bullous Dermatosis
Autoimmune disease characterized by subepidermal blisters and linear deposition of autoantibodies at the dermoepidermal junction. The accumulated autoantibodies are of IMMUNOG...<br/>Year introduced: 2013

MeSH
D062027 (1)
MeSH

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004099817	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Sep 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30847666, 35600473 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004099817

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Sep 13, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]

PMID:: 30847666
PMCID:: PMC6533346

Case Report: Family Curse: An SCN5A Mutation, c.611C>A, p.A204E Associated With a Family History of Dilated Cardiomyopathy and Arrhythmia.

Huang W, Xu R, Gao N, Wu X, Wen C.

Front Cardiovasc Med. 2022;9:822150. doi: 10.3389/fcvm.2022.822150. Erratum in: Front Cardiovasc Med. 2022 Jun 15;9:944834. doi: 10.3389/fcvm.2022.944834.

PubMed [citation]

PMID:: 35600473
PMCID:: PMC9120596

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004099817.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: PRKAG2 c.1114G>A (p.Asp372Asn) results in a conservative amino acid change located in the CBS domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251332 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1114G>A has been reported in the literature in an individual with arrhythmia (van Lint_2019) and in two individuals with dilated cardiomyopathy (DCM) combined with multifocal ectopic Purkinje-related premature contractions (MEPPC) who were also suspected of PRKAG2 syndrome and suffered sudden deaths, however they also harbored a putatively pathogenic variant in SCN5A which was found in other family members with DCM and MEPPC, and their father who also carried the variant of interest (but not the variant in SCN5A) was unaffected (Huang_2022). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 35600473, 30847666). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine