For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PAX6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr318Asnfs*23) 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 Genomic variation as it relates to human health
NM_001368894.2(PAX6):c.992dup (p.Thr332fs)
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.
(1)
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
1
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.992dup (p.Thr332fs)
Variation ID: 2940886 Accession: VCV002940886.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 11p13 11: 31793519-31793520 (GRCh38) [ NCBI UCSC ] 11: 31815067-31815068 (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 Feb 29, 2024 Feb 28, 2024 Oct 16, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001368894.2:c.992dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001355823.1:p.Thr332fs frameshift NM_000280.6:c.950dup NP_000271.1:p.Thr318fs frameshift NM_001127612.3:c.950dup NP_001121084.1:p.Thr318fs frameshift NM_001258462.3:c.992dup NP_001245391.1:p.Thr332fs frameshift NM_001258463.2:c.992dup NP_001245392.1:p.Thr332fs frameshift NM_001258464.2:c.950dup NP_001245393.1:p.Thr318fs frameshift NM_001258465.3:c.950dup NP_001245394.1:p.Thr318fs frameshift NM_001310158.2:c.992dup NP_001297087.1:p.Thr332fs frameshift NM_001310159.1:c.950dup NP_001297088.1:p.Thr318fs frameshift NM_001310160.2:c.542dup NP_001297089.1:p.Thr182fs frameshift NM_001310161.3:c.542dup NP_001297090.1:p.Thr182fs frameshift NM_001368887.2:c.950dup NP_001355816.1:p.Thr318fs frameshift NM_001368888.2:c.950dup NP_001355817.1:p.Thr318fs frameshift NM_001368889.2:c.950dup NP_001355818.1:p.Thr318fs frameshift NM_001368890.2:c.950dup NP_001355819.1:p.Thr318fs frameshift NM_001368891.2:c.950dup NP_001355820.1:p.Thr318fs frameshift NM_001368892.2:c.992dup NP_001355821.1:p.Thr332fs frameshift NM_001368893.2:c.992dup NP_001355822.1:p.Thr332fs frameshift NM_001368899.2:c.542dup NP_001355828.1:p.Thr182fs frameshift NM_001368900.2:c.542dup NP_001355829.1:p.Thr182fs frameshift NM_001368901.2:c.542dup NP_001355830.1:p.Thr182fs frameshift NM_001368902.2:c.542dup NP_001355831.1:p.Thr182fs frameshift NM_001368903.2:c.542dup NP_001355832.1:p.Thr182fs frameshift NM_001368904.2:c.542dup NP_001355833.1:p.Thr182fs frameshift NM_001368905.2:c.542dup NP_001355834.1:p.Thr182fs frameshift NM_001368906.2:c.542dup NP_001355835.1:p.Thr182fs frameshift NM_001368907.2:c.542dup NP_001355836.1:p.Thr182fs frameshift NM_001368908.2:c.542dup NP_001355837.1:p.Thr182fs frameshift NM_001368909.2:c.542dup NP_001355838.1:p.Thr182fs frameshift NM_001368910.2:c.1193dup NP_001355839.1:p.Thr399fs frameshift NM_001368911.2:c.995dup NP_001355840.1:p.Thr333fs frameshift NM_001368912.2:c.992dup NP_001355841.1:p.Thr332fs frameshift NM_001368913.2:c.992dup NP_001355842.1:p.Thr332fs frameshift NM_001368914.2:c.992dup NP_001355843.1:p.Thr332fs frameshift NM_001368915.2:c.950dup NP_001355844.1:p.Thr318fs frameshift NM_001368916.2:c.950dup NP_001355845.1:p.Thr318fs frameshift NM_001368917.2:c.950dup NP_001355846.1:p.Thr318fs frameshift NM_001368918.2:c.1067dup NP_001355847.1:p.Thr357fs frameshift NM_001368919.2:c.1067dup NP_001355848.1:p.Thr357fs frameshift NM_001368920.2:c.1025dup NP_001355849.1:p.Thr343fs frameshift NM_001368921.2:c.791dup NP_001355850.1:p.Thr265fs frameshift NM_001368922.2:c.791dup NP_001355851.1:p.Thr265fs frameshift NM_001368923.2:c.791dup NP_001355852.1:p.Thr265fs frameshift NM_001368924.2:c.791dup NP_001355853.1:p.Thr265fs frameshift NM_001368925.2:c.791dup NP_001355854.1:p.Thr265fs frameshift NM_001368926.2:c.791dup NP_001355855.1:p.Thr265fs frameshift NM_001368927.2:c.791dup NP_001355856.1:p.Thr265fs frameshift NM_001368928.2:c.749dup NP_001355857.1:p.Thr251fs frameshift NM_001368929.2:c.542dup NP_001355858.1:p.Thr182fs frameshift NM_001368930.2:c.347dup NP_001355859.1:p.Thr117fs frameshift NM_001604.6:c.992dup NP_001595.2:p.Thr332fs frameshift NR_160916.2:n.1331dup non-coding transcript variant NR_160917.2:n.1336dup non-coding transcript variant NC_000011.10:g.31793520dup NC_000011.9:g.31815068dup NG_008679.1:g.29442dup NG_159898.1:g.414dup LRG_720:g.29442dup LRG_720t1:c.950dup LRG_720p1:p.Thr318Asnfs - Protein change
- T117fs, T182fs, T399fs, T332fs, T333fs, T265fs, T343fs, T251fs, T318fs, T357fs
- Other names
- -
- Canonical SPDI
- NC_000011.10:31793519:C:CC
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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.
- -
- 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 |
698 | 902 | |
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
|
Oct 16, 2022 | RCV003792148.2 |
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
(Oct 16, 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: SCV004588363.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PAX6-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PAX6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr318Asnfs*23) 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). (less)
|
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:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PAX6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr318Asnfs*23) 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).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 this variant ...
HelpRecord last updated Sep 30, 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.