This frameshifting variant is found in the stop codon and is expected to extend the protein by 36 amino acids. This variant has been previously reported as a heterozygous change in patients with aniridia (PMID: 10477494, 25555363). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1309dupT (p.Ter437LeufsTer37) variant is classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001368894.2(PAX6):c.1309dup (p.Ter437LeuextTer?)
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, single submitter
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.1309dup (p.Ter437LeuextTer?)
Variation ID: 692032 Accession: VCV000692032.3
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 11p13 11: 31789935-31789936 (GRCh38) [ NCBI UCSC ] 11: 31811483-31811484 (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 Oct 20, 2019 Sep 23, 2023 Jun 28, 2018 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001368894.2:c.1309dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001355823.1:p.Ter437LeuextTer? frameshift stop lost NM_019040.5:c.*6412dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NM_000280.6:c.1267dup NP_000271.1:p.Ter423LeuextTer? frameshift stop lost NM_001127612.3:c.1267dup NP_001121084.1:p.Ter423LeuextTer? frameshift stop lost NM_001258462.3:c.1309dup NP_001245391.1:p.Ter437LeuextTer? frameshift stop lost NM_001258463.2:c.1309dup NP_001245392.1:p.Ter437LeuextTer? frameshift stop lost NM_001258464.2:c.1267dup NP_001245393.1:p.Ter423LeuextTer? frameshift stop lost NM_001258465.3:c.1267dup NP_001245394.1:p.Ter423LeuextTer? frameshift stop lost NM_001288725.2:c.*6398dup 3 prime UTR NM_001288726.2:c.*6507dup 3 prime UTR NM_001310158.2:c.1309dup NP_001297087.1:p.Ter437LeuextTer? frameshift stop lost NM_001310160.2:c.859dup NP_001297089.1:p.Ter287LeuextTer? frameshift stop lost NM_001310161.3:c.859dup NP_001297090.1:p.Ter287LeuextTer? frameshift stop lost NM_001368887.2:c.1267dup NP_001355816.1:p.Ter423LeuextTer? frameshift stop lost NM_001368888.2:c.1267dup NP_001355817.1:p.Ter423LeuextTer? frameshift stop lost NM_001368889.2:c.1267dup NP_001355818.1:p.Ter423LeuextTer? frameshift stop lost NM_001368890.2:c.1267dup NP_001355819.1:p.Ter423LeuextTer? frameshift stop lost NM_001368891.2:c.1267dup NP_001355820.1:p.Ter423LeuextTer? frameshift stop lost NM_001368892.2:c.1309dup NP_001355821.1:p.Ter437LeuextTer? frameshift stop lost NM_001368893.2:c.1309dup NP_001355822.1:p.Ter437LeuextTer? frameshift stop lost NM_001368899.2:c.859dup NP_001355828.1:p.Ter287LeuextTer? frameshift stop lost NM_001368900.2:c.859dup NP_001355829.1:p.Ter287LeuextTer? frameshift stop lost NM_001368901.2:c.859dup NP_001355830.1:p.Ter287LeuextTer? frameshift stop lost NM_001368902.2:c.859dup NP_001355831.1:p.Ter287LeuextTer? frameshift stop lost NM_001368903.2:c.859dup NP_001355832.1:p.Ter287LeuextTer? frameshift stop lost NM_001368904.2:c.859dup NP_001355833.1:p.Ter287LeuextTer? frameshift stop lost NM_001368905.2:c.859dup NP_001355834.1:p.Ter287LeuextTer? frameshift stop lost NM_001368906.2:c.859dup NP_001355835.1:p.Ter287LeuextTer? frameshift stop lost NM_001368907.2:c.859dup NP_001355836.1:p.Ter287LeuextTer? frameshift stop lost NM_001368908.2:c.859dup NP_001355837.1:p.Ter287LeuextTer? frameshift stop lost NM_001368909.2:c.859dup NP_001355838.1:p.Ter287LeuextTer? frameshift stop lost NM_001368910.2:c.1510dup NP_001355839.1:p.Ter504LeuextTer? frameshift stop lost NM_001368911.2:c.1161dup NP_001355840.1:p.Lys388Ter nonsense NM_001368912.2:c.1158dup NP_001355841.1:p.Lys387Ter nonsense NM_001368913.2:c.1158dup NP_001355842.1:p.Lys387Ter nonsense NM_001368914.2:c.1158dup NP_001355843.1:p.Lys387Ter nonsense NM_001368915.2:c.1116dup NP_001355844.1:p.Lys373Ter nonsense NM_001368916.2:c.1116dup NP_001355845.1:p.Lys373Ter nonsense NM_001368917.2:c.1116dup NP_001355846.1:p.Lys373Ter nonsense NM_001368918.2:c.1384dup NP_001355847.1:p.Ter462LeuextTer? frameshift stop lost NM_001368919.2:c.1384dup NP_001355848.1:p.Ter462LeuextTer? frameshift stop lost NM_001368920.2:c.1342dup NP_001355849.1:p.Ter448LeuextTer? frameshift stop lost NM_001368921.2:c.957dup NP_001355850.1:p.Lys320Ter nonsense NM_001368922.2:c.1108dup NP_001355851.1:p.Ter370LeuextTer? frameshift stop lost NM_001368923.2:c.1108dup NP_001355852.1:p.Ter370LeuextTer? frameshift stop lost NM_001368924.2:c.1108dup NP_001355853.1:p.Ter370LeuextTer? frameshift stop lost NM_001368925.2:c.1108dup NP_001355854.1:p.Ter370LeuextTer? frameshift stop lost NM_001368926.2:c.1108dup NP_001355855.1:p.Ter370LeuextTer? frameshift stop lost NM_001368927.2:c.1108dup NP_001355856.1:p.Ter370LeuextTer? frameshift stop lost NM_001368928.2:c.1066dup NP_001355857.1:p.Ter356LeuextTer? frameshift stop lost NM_001368929.2:c.708dup NP_001355858.1:p.Lys237Ter nonsense NM_001368930.2:c.664dup NP_001355859.1:p.Ter222LeuextTer? frameshift stop lost NM_001604.6:c.1309dup NP_001595.2:p.Ter437LeuextTer? frameshift stop lost NR_160916.2:n.1497dup non-coding transcript variant NR_160917.2:n.1653dup non-coding transcript variant NC_000011.10:g.31789936dup NC_000011.9:g.31811484dup NG_008679.1:g.33026dup NG_034086.2:g.285171dup LRG_720:g.33026dup LRG_720t1:c.1267dup LRG_720p1:p.Ter423Leufs - Protein change
- K387*, K388*, K237*, K320*, K373*
- Other names
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- Canonical SPDI
- NC_000011.10:31789935:A:AA
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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 | |
| ELP4 | - | - |
GRCh38 GRCh37 |
62 | 288 | |
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 (2) |
criteria provided, single submitter
|
Jun 28, 2018 | RCV000853307.2 |
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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Pathogenic
(Jun 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
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ANIRIDIA 1
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV000996161.1
First in ClinVar: Oct 20, 2019 Last updated: Oct 20, 2019 |
Comment:
This frameshifting variant is found in the stop codon and is expected to extend the protein by 36 amino acids. This variant has been previously … (more)
This frameshifting variant is found in the stop codon and is expected to extend the protein by 36 amino acids. This variant has been previously reported as a heterozygous change in patients with aniridia (PMID: 10477494, 25555363). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1309dupT (p.Ter437LeufsTer37) variant is classified as pathogenic. (less)
Number of individuals with the variant: 1
|
|
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not provided
(-)
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no classification provided
Method: literature only
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Aniridia 1
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV004036017.1
First in ClinVar: Sep 23, 2023 Last updated: Sep 23, 2023 |
|
Comment:
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:
This frameshifting variant is found in the stop codon and is expected to extend the protein by 36 amino acids. This variant has been previously reported as a heterozygous change in patients with aniridia (PMID: 10477494, 25555363). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1309dupT (p.Ter437LeufsTer37) variant is classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| PAX6-Related Aniridia. | Adam MP | - | 2018 | PMID: 20301534 |
| Clinical utility gene card for: Aniridia. | Richardson R | European journal of human genetics : EJHG | 2016 | PMID: 27381094 |
| Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations. | Hingorani M | Investigative ophthalmology & visual science | 2009 | PMID: 19218613 |
Text-mined citations for rs1592348310 ...
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 01, 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.