ClinVar Genomic variation as it relates to human health
NM_016203.4(PRKAG2):c.1625T>C (p.Val542Ala)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_016203.4(PRKAG2):c.1625T>C (p.Val542Ala)
Variation ID: 1776687 Accession: VCV001776687.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q36.1 7: 151560577 (GRCh38) [ NCBI UCSC ] 7: 151257663 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 29, 2022 May 1, 2024 Aug 15, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_016203.4:c.1625T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_057287.2:p.Val542Ala missense NM_001040633.2:c.1493T>C NP_001035723.1:p.Val498Ala missense NM_001304527.2:c.1250T>C NP_001291456.1:p.Val417Ala missense NM_001304531.2:c.902T>C NP_001291460.1:p.Val301Ala missense NM_001363698.2:c.1253T>C NP_001350627.1:p.Val418Ala missense NM_001407021.1:c.1625T>C NP_001393950.1:p.Val542Ala missense NM_001407022.1:c.1622T>C NP_001393951.1:p.Val541Ala missense NM_001407023.1:c.1622T>C NP_001393952.1:p.Val541Ala missense NM_001407024.1:c.1493T>C NP_001393953.1:p.Val498Ala missense NM_001407026.1:c.1490T>C NP_001393955.1:p.Val497Ala missense NM_001407027.1:c.1490T>C NP_001393956.1:p.Val497Ala missense NM_001407028.1:c.1253T>C NP_001393957.1:p.Val418Ala missense NM_001407029.1:c.1250T>C NP_001393958.1:p.Val417Ala missense NM_001407030.1:c.1337T>C NP_001393959.1:p.Val446Ala missense NM_001407031.1:c.1334T>C NP_001393960.1:p.Val445Ala missense NM_001407032.1:c.1307T>C NP_001393961.1:p.Val436Ala missense NM_001407033.1:c.1301T>C NP_001393962.1:p.Val434Ala missense NM_001407034.1:c.902T>C NP_001393963.1:p.Val301Ala missense NM_001407035.1:c.902T>C NP_001393964.1:p.Val301Ala missense NM_001407036.1:c.899T>C NP_001393965.1:p.Val300Ala missense NM_001407037.1:c.962T>C NP_001393966.1:p.Val321Ala missense NM_001407038.1:c.950T>C NP_001393967.1:p.Val317Ala missense NM_001407039.1:c.899T>C NP_001393968.1:p.Val300Ala missense NM_001407040.1:c.899T>C NP_001393969.1:p.Val300Ala missense NM_024429.2:c.902T>C NP_077747.1:p.Val301Ala missense NC_000007.14:g.151560577A>G NC_000007.13:g.151257663A>G NG_007486.2:g.321655T>C LRG_430:g.321655T>C LRG_430t1:c.1625T>C LRG_430p1:p.Val542Ala - Protein change
- V417A, V434A, V498A, V542A, V317A, V445A, V321A, V418A, V436A, V446A, V497A, V541A, V300A, V301A
- Other names
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- Canonical SPDI
- NC_000007.14:151560576:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PRKAG2 | No evidence available | No evidence available |
GRCh38 GRCh37 |
1133 | 1311 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Feb 24, 2021 | RCV002401145.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 4, 2022 | RCV003097025.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 15, 2023 | RCV004007343.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Feb 24, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002708947.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.V542A variant (also known as c.1625T>C), located in coding exon 15 of the PRKAG2 gene, results from a T to C substitution at nucleotide … (more)
The p.V542A variant (also known as c.1625T>C), located in coding exon 15 of the PRKAG2 gene, results from a T to C substitution at nucleotide position 1625. The valine at codon 542 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Jul 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lethal congenital glycogen storage disease of heart
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003247738.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 542 of the PRKAG2 protein (p.Val542Ala). … (more)
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 542 of the PRKAG2 protein (p.Val542Ala). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. This variant is present in population databases (rs757047965, gnomAD 0.006%). (less)
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Uncertain Significance
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004829114.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces valine with alanine at codon 542 of the PRKAG2 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces valine with alanine at codon 542 of the PRKAG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PRKAG2-related disorders in the literature. This variant has been identified in 2/251482 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. (less)
Number of individuals with the variant: 2
Zygosity: Single Heterozygote
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.