NM_016203.4(PRKAG2):c.1561G>A (p.Val521Met) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 16, 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:: RCV004010510.2

Allele description [Variation Report for NM_016203.4(PRKAG2):c.1561G>A (p.Val521Met)]

NM_016203.4(PRKAG2):c.1561G>A (p.Val521Met)

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.1561G>A (p.Val521Met)

HGVS:

NC_000007.14:g.151564101C>T
NG_007486.2:g.318131G>A
NM_001040633.2:c.1429G>A
NM_001304527.2:c.1186G>A
NM_001304531.2:c.838G>A
NM_001363698.2:c.1189G>A
NM_016203.4:c.1561G>AMANE SELECT
NM_024429.2:c.838G>A
NP_001035723.1:p.Val477Met
NP_001291456.1:p.Val396Met
NP_001291460.1:p.Val280Met
NP_001350627.1:p.Val397Met
NP_057287.2:p.Val521Met
NP_077747.1:p.Val280Met
LRG_430t1:c.1561G>A
LRG_430:g.318131G>A
LRG_430p1:p.Val521Met
NC_000007.13:g.151261187C>T
NC_000007.13:g.151261187C>T
NG_007486.1:g.318130G>A

Protein change:

V280M

Links:

dbSNP: rs767550594

NCBI 1000 Genomes Browser:

rs767550594

Molecular consequence:

NM_001040633.2:c.1429G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304527.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304531.2:c.838G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363698.2:c.1189G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016203.4:c.1561G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024429.2:c.838G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Biotoecus dicentrarchus G protein-coupled receptor 85 (GPR85) gene, partial cds
Biotoecus dicentrarchus G protein-coupled receptor 85 (GPR85) gene, partial cds
gi|1218185514|gb|MF175447.1|

Nucleotide
Salmo trutta m.fario Raw sequence reads (TaxID: 99804)
Salmo trutta m.fario Raw sequence reads (TaxID: 99804)
Salmo trutta m. fario Raw sequence reads

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004842204	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (May 16, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004842204

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(May 16, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

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 All of Us Research Program, National Institutes of Health, SCV004842204.1

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

Description

This missense variant replaces valine with methionine at codon 521 of the PRKAG2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251484 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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