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NM_016203.4(PRKAG2):c.997T>G (p.Ser333Ala) AND Cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 4, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000770262.6

Allele description [Variation Report for NM_016203.4(PRKAG2):c.997T>G (p.Ser333Ala)]

NM_016203.4(PRKAG2):c.997T>G (p.Ser333Ala)

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.997T>G (p.Ser333Ala)
HGVS:
  • NC_000007.14:g.151574899A>C
  • NG_007486.2:g.307333T>G
  • NM_001040633.2:c.865T>G
  • NM_001304527.2:c.622T>G
  • NM_001304531.2:c.274T>G
  • NM_001363698.2:c.625T>G
  • NM_016203.4:c.997T>GMANE SELECT
  • NM_024429.2:c.274T>G
  • NP_001035723.1:p.Ser289Ala
  • NP_001291456.1:p.Ser208Ala
  • NP_001291460.1:p.Ser92Ala
  • NP_001350627.1:p.Ser209Ala
  • NP_057287.2:p.Ser333Ala
  • NP_077747.1:p.Ser92Ala
  • LRG_430t1:c.997T>G
  • LRG_430:g.307333T>G
  • LRG_430p1:p.Ser333Ala
  • NC_000007.13:g.151271985A>C
  • NG_007486.1:g.307332T>G
  • NM_016203.3:c.997T>G
Protein change:
S208A
Links:
dbSNP: rs775005432
NCBI 1000 Genomes Browser:
rs775005432
Molecular consequence:
  • NM_001040633.2:c.865T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304527.2:c.622T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304531.2:c.274T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363698.2:c.625T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016203.4:c.997T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024429.2:c.274T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiomyopathy (CMYO)
Synonyms:
Cardiomyopathies
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000901694CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 22, 2016) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001357678Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 4, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The utility of the Mayo Score for predicting the yield of genetic testing in patients with hypertrophic cardiomyopathy.

Bonaventura J, Norambuena P, Tomašov P, Jindrová D, Šedivá H, Macek M Jr, Veselka J.

Arch Med Sci. 2019 May;15(3):641-649. doi: 10.5114/aoms.2018.78767. Epub 2018 Oct 8.

PubMed [citation]
PMID:
31110529
PMCID:
PMC6524174

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository, SCV000901694.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV001357678.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense variant replaces serine with alanine at codon 333 of the PRKAG2 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy, who also carried another pathogenic variant in the MYH7 gene (PMID: 31110529). This variant has been identified in 3/250994 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 24, 2024