Previously reported in association with anirida, however additional phenotypic details were not provided (Cross et al., 2020); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16712695, 34101622, 32360764)
ClinVar Genomic variation as it relates to human health
NM_001368894.2(PAX6):c.959-1G>A
Germline
Classification
Help
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.
(3)
Help
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/Likely pathogenic
3
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001368894.2(PAX6):c.959-1G>A
Variation ID: 800466 Accession: VCV000800466.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p13 11: 31815102 (GRCh37) [ NCBI UCSC ] 11: 31793554 (GRCh38) [ 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 23, 2019 Feb 28, 2024 Aug 28, 2023 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000011.10:31793553:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| PAX6 | Sufficient evidence for dosage pathogenicity | Little evidence for dosage pathogenicity |
GRCh38 GRCh37 |
695 | 899 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
no assertion criteria provided
|
Aug 15, 2019 | RCV000984447.2 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Aug 28, 2023 | RCV003325529.1 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 19, 2022 | RCV002549625.3 |
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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Likely pathogenic
(Aug 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV004031762.1
First in ClinVar: Sep 09, 2023 Last updated: Sep 09, 2023 |
Comment:
Previously reported in association with anirida, however additional phenotypic details were not provided (Cross et al., 2020); Canonical splice site variant predicted to result in … (more)
Previously reported in association with anirida, however additional phenotypic details were not provided (Cross et al., 2020); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16712695, 34101622, 32360764) (less)
|
|
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Pathogenic
(Jul 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
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
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003439718.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
This variant is also known as IVS10-1g>a. Disruption of this splice site has been observed in individual(s) with aniridia (PMID: 32360764). This variant is not … (more)
This variant is also known as IVS10-1g>a. Disruption of this splice site has been observed in individual(s) with aniridia (PMID: 32360764). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 10 of the PAX6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). ClinVar contains an entry for this variant (Variation ID: 800466). 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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|
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Pathogenic
(Aug 15, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Aniridia 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Wessex Regional Genetics Laboratory, Salisbury District Hospital
Accession: SCV001055806.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
|
Comment:
Comment:
This variant is also known as IVS10-1g>a. Disruption of this splice site has been observed in individual(s) with aniridia (PMID: 32360764). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 10 of the PAX6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). ClinVar contains an entry for this variant (Variation ID: 800466). 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.
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. |
Comment:
Previously reported in association with anirida, however additional phenotypic details were not provided (Cross et al., 2020); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16712695, 34101622, 32360764)
Comment:
This variant is also known as IVS10-1g>a. Disruption of this splice site has been observed in individual(s) with aniridia (PMID: 32360764). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 10 of the PAX6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). ClinVar contains an entry for this variant (Variation ID: 800466). 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Screening of a large PAX6 cohort identified many novel variants and emphasises the importance of the paired and homeobox domains. | Cross E | European journal of medical genetics | 2020 | PMID: 32360764 |
| Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
| Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects. | Vincent MC | European journal of human genetics : EJHG | 2003 | PMID: 12634864 |
Text-mined citations for rs1592412022 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record 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.