ClinVar Genomic variation as it relates to human health
NM_020320.5(RARS2):c.1390C>T (p.Gln464Ter)
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_020320.5(RARS2):c.1390C>T (p.Gln464Ter)
Variation ID: 1686119 Accession: VCV001686119.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q15 6: 87518655 (GRCh38) [ NCBI UCSC ] 6: 88228373 (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 May 28, 2022 Feb 14, 2024 Oct 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020320.5:c.1390C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_064716.2:p.Gln464Ter nonsense NM_001318785.2:c.865C>T NP_001305714.1:p.Gln289Ter nonsense NM_001350505.2:c.1390C>T NP_001337434.1:p.Gln464Ter nonsense NM_001350506.2:c.865C>T NP_001337435.1:p.Gln289Ter nonsense NM_001350507.2:c.865C>T NP_001337436.1:p.Gln289Ter nonsense NM_001350508.2:c.865C>T NP_001337437.1:p.Gln289Ter nonsense NM_001350509.2:c.865C>T NP_001337438.1:p.Gln289Ter nonsense NM_001350510.2:c.865C>T NP_001337439.1:p.Gln289Ter nonsense NM_001350511.2:c.865C>T NP_001337440.1:p.Gln289Ter nonsense NR_134857.2:n.1416C>T non-coding transcript variant NR_146738.2:n.1688C>T non-coding transcript variant NR_146739.2:n.1497C>T non-coding transcript variant NR_146740.2:n.1765C>T non-coding transcript variant NR_146741.2:n.1427C>T non-coding transcript variant NR_146742.2:n.1799C>T non-coding transcript variant NR_146743.2:n.1637C>T non-coding transcript variant NR_146744.2:n.1765C>T non-coding transcript variant NR_146745.2:n.1424C>T non-coding transcript variant NR_146746.2:n.1859C>T non-coding transcript variant NR_146747.2:n.1203C>T non-coding transcript variant NR_146748.2:n.1663C>T non-coding transcript variant NR_146749.2:n.1637C>T non-coding transcript variant NR_146750.2:n.1761C>T non-coding transcript variant NR_146751.2:n.1641C>T non-coding transcript variant NR_146752.2:n.1705C>T non-coding transcript variant NR_146753.2:n.1557C>T non-coding transcript variant NR_146754.2:n.1501C>T non-coding transcript variant NR_146755.2:n.1765C>T non-coding transcript variant NR_146756.2:n.1420C>T non-coding transcript variant NR_146757.2:n.1691C>T non-coding transcript variant NR_146758.2:n.1420C>T non-coding transcript variant NR_146759.2:n.1420C>T non-coding transcript variant NC_000006.12:g.87518655G>A NC_000006.11:g.88228373G>A NG_008601.1:g.76363C>T - Protein change
- Q289*, Q464*
- Other names
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- Canonical SPDI
- NC_000006.12:87518654:G:A
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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 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
- Links
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
Help
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
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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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RARS2 | - | - |
GRCh38 GRCh37 |
879 | 915 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 18, 2023 | RCV002250286.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 22, 2023 | RCV003094037.2 |
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
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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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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Pontocerebellar hypoplasia type 6
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002518959.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Nov 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Pontocerebellar hypoplasia type 6
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002588773.1
First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022 |
Comment:
The c.1390C>T;p.(Gln464*) variant creates a premature translational stop signal in the RARS2 gene. It is expected to result in an absent or disrupted protein product … (more)
The c.1390C>T;p.(Gln464*) variant creates a premature translational stop signal in the RARS2 gene. It is expected to result in an absent or disrupted protein product - PVS1. ClinVar contains an entry for this variant (Clinvar ID: 1686119) - PS4_supporting. The variant is present at low allele frequencies population databases (rs753312969 – gnomAD 0.00003990%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Likely pathogenic
(Oct 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pontocerebellar hypoplasia type 6
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004206134.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Feb 22, 2023)
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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: SCV003441225.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This variant is present in population databases (rs753312969, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RARS2-related … (more)
This variant is present in population databases (rs753312969, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1686119). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln464*) in the RARS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RARS2 are known to be pathogenic (PMID: 17847012, 22569581, 26083569). (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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Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations. | Lax NZ | Journal of neuropathology and experimental neurology | 2015 | PMID: 26083569 |
Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients. | Cassandrini D | Journal of inherited metabolic disease | 2013 | PMID: 22569581 |
Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. | Edvardson S | American journal of human genetics | 2007 | PMID: 17847012 |
Text-mined citations for rs753312969 ...
HelpRecord last updated Feb 20, 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.