Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32214788, 23860752)
ClinVar Genomic variation as it relates to human health
NM_001368894.2(PAX6):c.527G>A (p.Trp176Ter)
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.
(2)
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
2
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.527G>A (p.Trp176Ter)
Variation ID: 942257 Accession: VCV000942257.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p13 11: 31800729 (GRCh38) [ NCBI UCSC ] 11: 31822277 (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 Jul 16, 2020 Feb 28, 2024 Oct 19, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001368894.2:c.527G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001355823.1:p.Trp176Ter nonsense NM_000280.6:c.485G>A NP_000271.1:p.Trp162Ter nonsense NM_001127612.3:c.485G>A NP_001121084.1:p.Trp162Ter nonsense NM_001258462.3:c.527G>A NP_001245391.1:p.Trp176Ter nonsense NM_001258463.2:c.527G>A NP_001245392.1:p.Trp176Ter nonsense NM_001258464.2:c.485G>A NP_001245393.1:p.Trp162Ter nonsense NM_001258465.3:c.485G>A NP_001245394.1:p.Trp162Ter nonsense NM_001310158.2:c.527G>A NP_001297087.1:p.Trp176Ter nonsense NM_001310159.1:c.485G>A NP_001297088.1:p.Trp162Ter nonsense NM_001310160.2:c.77G>A NP_001297089.1:p.Trp26Ter nonsense NM_001310161.3:c.77G>A NP_001297090.1:p.Trp26Ter nonsense NM_001368887.2:c.485G>A NP_001355816.1:p.Trp162Ter nonsense NM_001368888.2:c.485G>A NP_001355817.1:p.Trp162Ter nonsense NM_001368889.2:c.485G>A NP_001355818.1:p.Trp162Ter nonsense NM_001368890.2:c.485G>A NP_001355819.1:p.Trp162Ter nonsense NM_001368891.2:c.485G>A NP_001355820.1:p.Trp162Ter nonsense NM_001368892.2:c.527G>A NP_001355821.1:p.Trp176Ter nonsense NM_001368893.2:c.527G>A NP_001355822.1:p.Trp176Ter nonsense NM_001368899.2:c.77G>A NP_001355828.1:p.Trp26Ter nonsense NM_001368900.2:c.77G>A NP_001355829.1:p.Trp26Ter nonsense NM_001368901.2:c.77G>A NP_001355830.1:p.Trp26Ter nonsense NM_001368902.2:c.77G>A NP_001355831.1:p.Trp26Ter nonsense NM_001368903.2:c.77G>A NP_001355832.1:p.Trp26Ter nonsense NM_001368904.2:c.77G>A NP_001355833.1:p.Trp26Ter nonsense NM_001368905.2:c.77G>A NP_001355834.1:p.Trp26Ter nonsense NM_001368906.2:c.77G>A NP_001355835.1:p.Trp26Ter nonsense NM_001368907.2:c.77G>A NP_001355836.1:p.Trp26Ter nonsense NM_001368908.2:c.77G>A NP_001355837.1:p.Trp26Ter nonsense NM_001368909.2:c.77G>A NP_001355838.1:p.Trp26Ter nonsense NM_001368910.2:c.728G>A NP_001355839.1:p.Trp243Ter nonsense NM_001368911.2:c.530G>A NP_001355840.1:p.Trp177Ter nonsense NM_001368912.2:c.527G>A NP_001355841.1:p.Trp176Ter nonsense NM_001368913.2:c.527G>A NP_001355842.1:p.Trp176Ter nonsense NM_001368914.2:c.527G>A NP_001355843.1:p.Trp176Ter nonsense NM_001368915.2:c.485G>A NP_001355844.1:p.Trp162Ter nonsense NM_001368916.2:c.485G>A NP_001355845.1:p.Trp162Ter nonsense NM_001368917.2:c.485G>A NP_001355846.1:p.Trp162Ter nonsense NM_001368918.2:c.602G>A NP_001355847.1:p.Trp201Ter nonsense NM_001368919.2:c.602G>A NP_001355848.1:p.Trp201Ter nonsense NM_001368920.2:c.560G>A NP_001355849.1:p.Trp187Ter nonsense NM_001368921.2:c.326G>A NP_001355850.1:p.Trp109Ter nonsense NM_001368922.2:c.326G>A NP_001355851.1:p.Trp109Ter nonsense NM_001368923.2:c.326G>A NP_001355852.1:p.Trp109Ter nonsense NM_001368924.2:c.326G>A NP_001355853.1:p.Trp109Ter nonsense NM_001368925.2:c.326G>A NP_001355854.1:p.Trp109Ter nonsense NM_001368926.2:c.326G>A NP_001355855.1:p.Trp109Ter nonsense NM_001368927.2:c.326G>A NP_001355856.1:p.Trp109Ter nonsense NM_001368928.2:c.284G>A NP_001355857.1:p.Trp95Ter nonsense NM_001368929.2:c.77G>A NP_001355858.1:p.Trp26Ter nonsense NM_001604.6:c.527G>A NP_001595.2:p.Trp176Ter nonsense NR_160916.2:n.949G>A non-coding transcript variant NR_160917.2:n.954G>A non-coding transcript variant NC_000011.10:g.31800729C>T NC_000011.9:g.31822277C>T NG_008679.1:g.22233G>A LRG_720:g.22233G>A LRG_720t1:c.485G>A - Protein change
- W243*, W162*, W176*, W187*, W26*, W95*, W109*, W201*, W177*
- Other names
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- Canonical SPDI
- NC_000011.10:31800728:C:T
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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.
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- 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) |
criteria provided, single submitter
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Oct 19, 2022 | RCV001212207.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 20, 2020 | RCV001546575.2 |
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
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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|---|---|---|---|---|---|
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Pathogenic
(Jan 20, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001766113.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32214788, 23860752) (less)
|
|
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Pathogenic
(Oct 19, 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
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001383784.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 28, 2024 |
Comment:
This premature translational stop signal has been observed in individual(s) with aniridia (PMID: 32214788). This variant is not present in population databases (gnomAD no frequency). … (more)
This premature translational stop signal has been observed in individual(s) with aniridia (PMID: 32214788). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp162*) in the PAX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). ClinVar contains an entry for this variant (Variation ID: 942257). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. (less)
|
Comment:
Comment:
This premature translational stop signal has been observed in individual(s) with aniridia (PMID: 32214788). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp162*) in the PAX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). ClinVar contains an entry for this variant (Variation ID: 942257). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.
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:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32214788, 23860752)
Comment:
This premature translational stop signal has been observed in individual(s) with aniridia (PMID: 32214788). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp162*) in the PAX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). ClinVar contains an entry for this variant (Variation ID: 942257). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutation spectrum of PAX6 and clinical findings in 95 Chinese patients with aniridia. | You B | Molecular vision | 2020 | PMID: 32214788 |
| 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 rs1953478890 ...
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.