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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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004099817Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Sep 13, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024