ClinVar Genomic variation as it relates to human health
NM_001368894.2(PAX6):c.202A>C (p.Ser68Arg)
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.202A>C (p.Ser68Arg)
Variation ID: 3024451 Accession: VCV003024451.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p13 11: 31801758 (GRCh38) [ NCBI UCSC ] 11: 31823306 (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 Mar 11, 2024 Mar 10, 2024 Mar 1, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001368894.2:c.202A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001355823.1:p.Ser68Arg missense NM_000280.6:c.160A>C NP_000271.1:p.Ser54Arg missense NM_001127612.3:c.160A>C NP_001121084.1:p.Ser54Arg missense NM_001258462.3:c.202A>C NP_001245391.1:p.Ser68Arg missense NM_001258463.2:c.202A>C NP_001245392.1:p.Ser68Arg missense NM_001258464.2:c.160A>C NP_001245393.1:p.Ser54Arg missense NM_001258465.3:c.160A>C NP_001245394.1:p.Ser54Arg missense NM_001310158.2:c.202A>C NP_001297087.1:p.Ser68Arg missense NM_001310159.1:c.160A>C NP_001297088.1:p.Ser54Arg missense NM_001310160.2:c.-580A>C 5 prime UTR NM_001310161.3:c.-249A>C 5 prime UTR NM_001368887.2:c.160A>C NP_001355816.1:p.Ser54Arg missense NM_001368888.2:c.160A>C NP_001355817.1:p.Ser54Arg missense NM_001368889.2:c.160A>C NP_001355818.1:p.Ser54Arg missense NM_001368890.2:c.160A>C NP_001355819.1:p.Ser54Arg missense NM_001368891.2:c.160A>C NP_001355820.1:p.Ser54Arg missense NM_001368892.2:c.202A>C NP_001355821.1:p.Ser68Arg missense NM_001368893.2:c.202A>C NP_001355822.1:p.Ser68Arg missense NM_001368899.2:c.-249A>C 5 prime UTR NM_001368900.2:c.-249A>C 5 prime UTR NM_001368901.2:c.-249A>C 5 prime UTR NM_001368902.2:c.-580A>C 5 prime UTR NM_001368903.2:c.-249A>C 5 prime UTR NM_001368904.2:c.-249A>C 5 prime UTR NM_001368905.2:c.-580A>C 5 prime UTR NM_001368906.2:c.-249A>C 5 prime UTR NM_001368907.2:c.-249A>C 5 prime UTR NM_001368908.2:c.-249A>C 5 prime UTR NM_001368909.2:c.-249A>C 5 prime UTR NM_001368910.2:c.403A>C NP_001355839.1:p.Ser135Arg missense NM_001368911.2:c.205A>C NP_001355840.1:p.Ser69Arg missense NM_001368912.2:c.202A>C NP_001355841.1:p.Ser68Arg missense NM_001368913.2:c.202A>C NP_001355842.1:p.Ser68Arg missense NM_001368914.2:c.202A>C NP_001355843.1:p.Ser68Arg missense NM_001368915.2:c.160A>C NP_001355844.1:p.Ser54Arg missense NM_001368916.2:c.160A>C NP_001355845.1:p.Ser54Arg missense NM_001368917.2:c.160A>C NP_001355846.1:p.Ser54Arg missense NM_001368918.2:c.277A>C NP_001355847.1:p.Ser93Arg missense NM_001368919.2:c.277A>C NP_001355848.1:p.Ser93Arg missense NM_001368920.2:c.235A>C NP_001355849.1:p.Ser79Arg missense NM_001368921.2:c.198+4A>C intron variant NM_001368922.2:c.198+4A>C intron variant NM_001368923.2:c.198+4A>C intron variant NM_001368924.2:c.198+4A>C intron variant NM_001368925.2:c.198+4A>C intron variant NM_001368926.2:c.198+4A>C intron variant NM_001368927.2:c.198+4A>C intron variant NM_001368928.2:c.156+4A>C intron variant NM_001368929.2:c.-249A>C 5 prime UTR NM_001604.6:c.202A>C NP_001595.2:p.Ser68Arg missense NR_160916.2:n.624A>C non-coding transcript variant NR_160917.2:n.629A>C non-coding transcript variant NC_000011.10:g.31801758T>G NC_000011.9:g.31823306T>G NG_008679.1:g.21204A>C LRG_720:g.21204A>C LRG_720t1:c.160A>C LRG_720p1:p.Ser54Arg - Protein change
- S54R, S135R, S68R, S69R, S79R, S93R
- Other names
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PAX6, SER54ARG, 160A-C
- Canonical SPDI
- NC_000011.10:31801757:T: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
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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 |
698 | 902 | |
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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| Pathogenic (1) |
no assertion criteria provided
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Mar 1, 2024 | RCV003883476.1 |
Submissions - Germline
| Classification
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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
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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
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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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Pathogenic
(Mar 01, 2024)
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no assertion criteria provided
Method: literature only
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MICROPHTHALMIA/COLOBOMA 12
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV004697966.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
Comment on evidence:
In a 7-month-old boy (patient 3189 in the Human Genetics Unit eye malformation cohort) with severe bilateral microphthalmia and sclerocornea, who also had right congenital … (more)
In a 7-month-old boy (patient 3189 in the Human Genetics Unit eye malformation cohort) with severe bilateral microphthalmia and sclerocornea, who also had right congenital aphakia and small left lens presenting as a hypodense attachment to the cornea (MCOPCB12; 120200), who was negative for mutation in the SOX2 (184429) and OTX2 (600037) genes, Williamson et al. (2020) identified heterozygosity for a de novo c.160A-C transversion (c.160A-C, NM_000280.4) in the PAX6 gene, resulting in a ser54-to-arg (S54R) substitution within the highly conserved paired domain. His unaffected parents and brother did not carry the mutation. EMSA analysis demonstrated an 85% reduction in binding of the S54R mutant to LE9 and SIMO elements, known DNA targets of PAX6, compared to the wildtype protein. (less)
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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 |
|---|---|---|---|---|
| Recurrent heterozygous PAX6 missense variants cause severe bilateral microphthalmia via predictable effects on DNA-protein interaction. | Williamson KA | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31700164 |
Text-mined citations for this variant ...
HelpRecord last updated Nov 25, 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.