ClinVar Genomic variation as it relates to human health
NM_001368894.2(PAX6):c.52G>C (p.Gly18Arg)
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_001368894.2(PAX6):c.52G>C (p.Gly18Arg)
Variation ID: 289849 Accession: VCV000289849.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p13 11: 31802793 (GRCh38) [ NCBI UCSC ] 11: 31824341 (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 Dec 6, 2016 Feb 28, 2024 Nov 10, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001368894.2:c.52G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001355823.1:p.Gly18Arg missense NM_000280.6:c.52G>C NP_000271.1:p.Gly18Arg missense NM_001127612.3:c.52G>C NP_001121084.1:p.Gly18Arg missense NM_001258462.3:c.52G>C NP_001245391.1:p.Gly18Arg missense NM_001258463.2:c.52G>C NP_001245392.1:p.Gly18Arg missense NM_001258464.2:c.52G>C NP_001245393.1:p.Gly18Arg missense NM_001258465.3:c.52G>C NP_001245394.1:p.Gly18Arg missense NM_001310158.2:c.52G>C NP_001297087.1:p.Gly18Arg missense NM_001310159.1:c.52G>C NP_001297088.1:p.Gly18Arg missense NM_001310160.2:c.-730G>C 5 prime UTR NM_001310161.3:c.-399G>C 5 prime UTR NM_001368887.2:c.52G>C NP_001355816.1:p.Gly18Arg missense NM_001368888.2:c.52G>C NP_001355817.1:p.Gly18Arg missense NM_001368889.2:c.52G>C NP_001355818.1:p.Gly18Arg missense NM_001368890.2:c.52G>C NP_001355819.1:p.Gly18Arg missense NM_001368891.2:c.52G>C NP_001355820.1:p.Gly18Arg missense NM_001368892.2:c.52G>C NP_001355821.1:p.Gly18Arg missense NM_001368893.2:c.52G>C NP_001355822.1:p.Gly18Arg missense NM_001368899.2:c.-357G>C 5 prime UTR NM_001368900.2:c.-399G>C 5 prime UTR NM_001368901.2:c.-357G>C 5 prime UTR NM_001368902.2:c.-688G>C 5 prime UTR NM_001368903.2:c.-399G>C 5 prime UTR NM_001368904.2:c.-267-1017G>C intron variant NM_001368905.2:c.-730G>C 5 prime UTR NM_001368906.2:c.-357G>C 5 prime UTR NM_001368907.2:c.-357G>C 5 prime UTR NM_001368908.2:c.-399G>C 5 prime UTR NM_001368909.2:c.-267-1017G>C intron variant NM_001368910.2:c.295G>C NP_001355839.1:p.Gly99Arg missense NM_001368911.2:c.55G>C NP_001355840.1:p.Gly19Arg missense NM_001368912.2:c.52G>C NP_001355841.1:p.Gly18Arg missense NM_001368913.2:c.52G>C NP_001355842.1:p.Gly18Arg missense NM_001368914.2:c.52G>C NP_001355843.1:p.Gly18Arg missense NM_001368915.2:c.52G>C NP_001355844.1:p.Gly18Arg missense NM_001368916.2:c.52G>C NP_001355845.1:p.Gly18Arg missense NM_001368917.2:c.52G>C NP_001355846.1:p.Gly18Arg missense NM_001368918.2:c.52G>C NP_001355847.1:p.Gly18Arg missense NM_001368919.2:c.52G>C NP_001355848.1:p.Gly18Arg missense NM_001368920.2:c.52G>C NP_001355849.1:p.Gly18Arg missense NM_001368921.2:c.52G>C NP_001355850.1:p.Gly18Arg missense NM_001368922.2:c.52G>C NP_001355851.1:p.Gly18Arg missense NM_001368923.2:c.52G>C NP_001355852.1:p.Gly18Arg missense NM_001368924.2:c.52G>C NP_001355853.1:p.Gly18Arg missense NM_001368925.2:c.52G>C NP_001355854.1:p.Gly18Arg missense NM_001368926.2:c.52G>C NP_001355855.1:p.Gly18Arg missense NM_001368927.2:c.52G>C NP_001355856.1:p.Gly18Arg missense NM_001368928.2:c.52G>C NP_001355857.1:p.Gly18Arg missense NM_001368929.2:c.-399G>C 5 prime UTR NM_001604.6:c.52G>C NP_001595.2:p.Gly18Arg missense NR_160916.2:n.474G>C non-coding transcript variant NR_160917.2:n.521G>C non-coding transcript variant NC_000011.10:g.31802793C>G NC_000011.9:g.31824341C>G NG_008679.1:g.20169G>C LRG_720:g.20169G>C - Protein change
- G18R, G99R, G19R
- Other names
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- Canonical SPDI
- NC_000011.10:31802792:C: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
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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
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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| PAX6 | Sufficient evidence for dosage pathogenicity | Little evidence for dosage pathogenicity |
GRCh38 GRCh37 |
695 | 899 | |
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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| Likely pathogenic (1) |
criteria provided, single submitter
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Aug 2, 2016 | RCV000317485.4 | |
| Pathogenic (1) |
criteria provided, single submitter
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May 21, 2022 | RCV000635404.8 | |
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PAX6-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Nov 10, 2023 | RCV003401272.1 |
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
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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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Likely pathogenic
(Aug 02, 2016)
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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: SCV000344276.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(May 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Aniridia 1
Irido-corneo-trabecular dysgenesis
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000756817.5
First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly18 amino acid residue in PAX6. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly18 amino acid residue in PAX6. Other variant(s) that disrupt this residue have been observed in individuals with PAX6-related conditions (PMID: 9792406), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects PAX6 function (PMID: 15579687, 20577777). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PAX6 protein function. ClinVar contains an entry for this variant (Variation ID: 289849). This missense change has been observed in individual(s) with PAX6-related disease (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 18 of the PAX6 protein (p.Gly18Arg). (less)
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Pathogenic
(Nov 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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PAX6-related disorder
Affected status: yes
Allele origin:
unknown
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Daryl Scott Lab, Baylor College of Medicine
Accession: SCV004102722.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
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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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Pax6 localizes to chromatin-rich territories and displays a slow nuclear mobility altered by disease mutations. | Elvenes J | Cellular and molecular life sciences : CMLS | 2010 | PMID: 20577777 |
| Genetic analysis of the Caenorhabditis elegans pax-6 locus: roles of paired domain-containing and nonpaired domain-containing isoforms. | Cinar HN | Genetics | 2004 | PMID: 15579687 |
| PAX6 in sensory development. | van Heyningen V | Human molecular genetics | 2002 | PMID: 12015275 |
| Ten novel mutations found in Aniridia. | Wolf MT | Human mutation | 1998 | PMID: 9792406 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PAX6 | - | - | - | - |
| I:\T\Papers and Publications\PAX6\Kim_2008.pdf | - | - | - | - |
Text-mined citations for rs886044289 ...
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.