ClinVar Genomic variation as it relates to human health
NM_020320.5(RARS2):c.-2A>G
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.
Pathogenic(1); Likely pathogenic(2); Uncertain significance(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_020320.5(RARS2):c.-2A>G
Variation ID: 802251 Accession: VCV000802251.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q15 6: 87589959 (GRCh38) [ NCBI UCSC ] 6: 88299677 (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 17, 2014 Dec 30, 2023 Oct 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020320.5:c.-2A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
5 prime UTR NM_001318785.2:c.-692A>G 5 prime UTR NM_001350505.2:c.-2A>G 5 prime UTR NM_001350506.2:c.-748A>G 5 prime UTR NM_001350507.2:c.-871A>G 5 prime UTR NM_001350508.2:c.-910A>G 5 prime UTR NM_001350509.2:c.-618A>G 5 prime UTR NM_001350510.2:c.-748A>G 5 prime UTR NM_001350511.2:c.-867A>G 5 prime UTR NR_134857.2:n.29A>G non-coding transcript variant NR_146738.2:n.29A>G non-coding transcript variant NR_146739.2:n.29A>G non-coding transcript variant NR_146740.2:n.29A>G non-coding transcript variant NR_146741.2:n.29A>G non-coding transcript variant NR_146742.2:n.29A>G non-coding transcript variant NR_146743.2:n.29A>G non-coding transcript variant NR_146744.2:n.29A>G non-coding transcript variant NR_146745.2:n.29A>G non-coding transcript variant NR_146746.2:n.29A>G non-coding transcript variant NR_146747.2:n.29A>G non-coding transcript variant NR_146748.2:n.29A>G non-coding transcript variant NR_146749.2:n.29A>G non-coding transcript variant NR_146750.2:n.29A>G non-coding transcript variant NR_146751.2:n.29A>G non-coding transcript variant NR_146752.2:n.29A>G non-coding transcript variant NR_146753.2:n.29A>G non-coding transcript variant NR_146754.2:n.29A>G non-coding transcript variant NR_146755.2:n.29A>G non-coding transcript variant NR_146756.2:n.29A>G non-coding transcript variant NR_146757.2:n.29A>G non-coding transcript variant NR_146758.2:n.29A>G non-coding transcript variant NR_146759.2:n.29A>G non-coding transcript variant NC_000006.12:g.87589959T>C NC_000006.11:g.88299677T>C NG_008601.1:g.5059A>G NG_108712.1:g.943T>C - Protein change
- Other names
- -2A-G
- Canonical SPDI
- NC_000006.12:87589958:T: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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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
Help
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
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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RARS2 | - | - |
GRCh38 GRCh37 |
879 | 915 |
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
Help
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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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Feb 22, 2023 | RCV000118121.10 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 3, 2023 | RCV000987753.4 |
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
(Aug 05, 2013)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000152465.1
First in ClinVar: May 17, 2014 Last updated: May 17, 2014 |
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Pathogenic
(May 28, 2019)
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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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Mendelics
Accession: SCV001137195.1
First in ClinVar: Jan 11, 2020 Last updated: Jan 11, 2020 |
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Uncertain significance
(Oct 03, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV002817214.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
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Likely pathogenic
(Feb 22, 2023)
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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: SCV004030838.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023 |
Comment:
Published functional studies suggest a damaging effect on promoter activity (Li et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); This … (more)
Published functional studies suggest a damaging effect on promoter activity (Li et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33587123, 28534666, 34717047, 25809939) (less)
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Likely pathogenic
(Oct 03, 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: SCV004206147.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jul 01, 2015)
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no assertion criteria provided
Method: literature only
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PONTOCEREBELLAR HYPOPLASIA, TYPE 6
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000243944.2
First in ClinVar: Aug 16, 2015 Last updated: Oct 09, 2016 |
Comment on evidence:
In 2 Hispanic sibs with pontocerebellar hypoplasia type 6 (PCH6; 611523), Li et al. (2015) identified a homozygous -2A-G transition in the promoter of the … (more)
In 2 Hispanic sibs with pontocerebellar hypoplasia type 6 (PCH6; 611523), Li et al. (2015) identified a homozygous -2A-G transition in the promoter of the RARS2 gene. The mutation, which segregated with the disorder in the family, was not found in the 1000 Genomes Project or Exome Sequencing Project databases. Patient cells showed decreased expression of RARS2 compared to controls, and luciferase studies in HEK293 cells transfected with the mutation showed a 40% reduction of promoter activity compared to wildtype. (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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A novel mutation in the promoter of RARS2 causes pontocerebellar hypoplasia in two siblings. | Li Z | Journal of human genetics | 2015 | PMID: 25809939 |
Text-mined citations for rs201150141 ...
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.