ClinVar Genomic variation as it relates to human health
NM_001377295.2(GNAT2):c.937C>T (p.Arg313Ter)
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_001377295.2(GNAT2):c.937C>T (p.Arg313Ter)
Variation ID: 623285 Accession: VCV000623285.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p13.3 1: 109603482 (GRCh38) [ NCBI UCSC ] 1: 110146104 (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 Mar 25, 2019 Feb 14, 2024 Nov 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001377295.2:c.937C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001364224.1:p.Arg313Ter nonsense NM_001379232.1:c.937C>T NP_001366161.1:p.Arg313Ter nonsense NM_005272.5:c.937C>T NP_005263.1:p.Arg313Ter nonsense NC_000001.11:g.109603482G>A NC_000001.10:g.110146104G>A NG_009099.1:g.14602C>T - Protein change
- R313*
- Other names
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- Canonical SPDI
- NC_000001.11:109603481: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
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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
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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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GNAT2 | - | - |
GRCh38 GRCh37 |
198 | 241 |
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
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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 (2) |
criteria provided, single submitter
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Jun 24, 2022 | RCV000761410.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 8, 2023 | RCV003558561.1 |
Submissions - Germline
Classification
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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
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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
(Nov 08, 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: SCV004291968.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg313*) in the GNAT2 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg313*) in the GNAT2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the GNAT2 protein. This variant is present in population databases (rs748981899, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with achromatopsia (PMID: 21107338). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 623285). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Achromatopsia 4
(Autosomal recessive inheritance)
Affected status: no
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002557753.1
First in ClinVar: Aug 08, 2022 Last updated: Aug 08, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with achromatopsia 4 (MIM#613856). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (3 heterozygotes, 0 homozygotes). (SP) 0601 - Variant results in the loss of the well-established functional GTP binding domain, conserved motif and GTP, Mg2+ and receptor-binding residues (NCBI domains, PMID: 31058429, PMID: 18643908). (I) 0704 - Other protein truncation variants comparable to the one identified in this case has limited previous evidence for pathogenicity. One variant, p.(Ile319fs*5), has been reported as pathogenic and observed in compound heterozygous siblings with achromatopsia (PMID: 31058429, ClinVar). p.(Tyr320*) has been reported as pathogenic (LOVD). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as likely pathogenic and observed in two unrelated homozygous individuals with congenital achromatopsia or cone dystrophy, and a compound heterozygous individual with achromatopsia (ClinVar, PMID: 21107338, PMID: 27208204, PMID: 31058429). (SP) 0906 - Segregation evidence for this variant is inconclusive. Segregation testing demonstrated that all affected individuals in a large family shared the same homozygous haplotype, whereas unaffected relatives did not. These findings were considered inconclusive (PMID: 21107338). (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Likely pathogenic
(Jun 12, 2018)
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no assertion criteria provided
Method: research
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Achromatopsia 4
Affected status: yes
Allele origin:
germline
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Molecular Genetics Laboratory, Institute for Ophthalmic Research
Accession: SCV000891394.1
First in ClinVar: Mar 25, 2019 Last updated: Mar 25, 2019 |
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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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Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene. | Felden J | Human mutation | 2019 | PMID: 31058429 |
Molecular findings from 537 individuals with inherited retinal disease. | Ellingford JM | Journal of medical genetics | 2016 | PMID: 27208204 |
Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene. | Ouechtati F | Journal of human genetics | 2011 | PMID: 21107338 |
G protein subtype specificity of rhodopsin intermediates metarhodopsin Ib and metarhodopsin II. | Morizumi T | Photochemistry and photobiology | 2009 | PMID: 18643908 |
Text-mined citations for rs748981899 ...
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.