ClinVar Genomic variation as it relates to human health
NM_145691.4(ATPAF2):c.40C>G (p.Arg14Gly)
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_145691.4(ATPAF2):c.40C>G (p.Arg14Gly)
Variation ID: 214135 Accession: VCV000214135.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p11.2 17: 18038974 (GRCh38) [ NCBI UCSC ] 17: 17942288 (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 Jun 8, 2016 May 1, 2024 Nov 18, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_145691.4:c.40C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_663729.1:p.Arg14Gly missense NC_000017.11:g.18038974G>C NC_000017.10:g.17942288G>C NG_012824.1:g.5193C>G - Protein change
- R14G
- Other names
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- Canonical SPDI
- NC_000017.11:18038973:G:C
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00026
Exome Aggregation Consortium (ExAC) 0.00027
The Genome Aggregation Database (gnomAD) 0.00040
Trans-Omics for Precision Medicine (TOPMed) 0.00046
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00062
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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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ATPAF2 | - | - |
GRCh38 GRCh37 |
155 | 302 |
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
Help
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 (4) |
criteria provided, multiple submitters, no conflicts
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Jul 25, 2022 | RCV000224495.10 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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May 11, 2018 | RCV000305929.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 18, 2022 | RCV004020390.1 |
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
Help
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
(May 11, 2018)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1
Affected status: yes
Allele origin:
paternal
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Baylor Genetics
Accession: SCV001527464.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Uncertain significance
(Jul 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002203100.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 14 of the ATPAF2 protein (p.Arg14Gly). … (more)
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 14 of the ATPAF2 protein (p.Arg14Gly). This variant is present in population databases (rs143241583, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ATPAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 214135). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. (less)
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Uncertain significance
(Nov 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV004912294.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.40C>G (p.R14G) alteration is located in exon 1 (coding exon 1) of the ATPAF2 gene. This alteration results from a C to G substitution … (more)
The c.40C>G (p.R14G) alteration is located in exon 1 (coding exon 1) of the ATPAF2 gene. This alteration results from a C to G substitution at nucleotide position 40, causing the arginine (R) at amino acid position 14 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Uncertain Significance
(May 05, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281451.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Comment:
Converted during submission to Uncertain significance.
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Uncertain significance
(Apr 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000860716.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Dec 20, 2017)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000251167.5
First in ClinVar: Oct 11, 2015 Last updated: Sep 26, 2017 |
Comment:
The R14G variant in the ATPAF2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more)
The R14G variant in the ATPAF2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R14G variant is observed in 21/50220 alleles (0.042%) from individuals of European (Non-Finnish) background in the ExAC dataset (Lek et al., 2016). The R14G variant is a non-conservative amino acid substitution, which occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R14G as a variant of uncertain significance. (less)
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Uncertain significance
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000401077.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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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
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATPAF2 | - | - | - | - |
Text-mined citations for rs143241583 ...
HelpRecord last updated May 08, 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.