ClinVar Genomic variation as it relates to human health
NM_000278.5(PAX2):c.685C>T (p.Arg229Ter)
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_000278.5(PAX2):c.685C>T (p.Arg229Ter)
Variation ID: 156294 Accession: VCV000156294.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q24.31 10: 100806498 (GRCh38) [ NCBI UCSC ] 10: 102566255 (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 6, 2014 Feb 28, 2024 Feb 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000278.5:c.685C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000269.3:p.Arg229Ter nonsense NM_001304569.2:c.778C>T NP_001291498.1:p.Arg260Ter nonsense NM_003987.5:c.754C>T NP_003978.3:p.Arg252Ter nonsense NM_003988.5:c.685C>T NP_003979.2:p.Arg229Ter nonsense NM_003989.5:c.685C>T NP_003980.3:p.Arg229Ter nonsense NM_003990.5:c.754C>T NP_003981.3:p.Arg252Ter nonsense NC_000010.11:g.100806498C>T NC_000010.10:g.102566255C>T NG_008680.2:g.75790C>T - Protein change
- R229*, R252*, R260*
- Other names
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- Canonical SPDI
- NC_000010.11:100806497: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
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The frequency of the allele represented by this VCV record.
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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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PAX2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
435 | 455 |
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
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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 (2) |
criteria provided, single submitter
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Jun 17, 2021 | RCV000144378.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 5, 2022 | RCV001813758.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 8, 2023 | RCV002498654.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 3, 2022 | RCV001808402.1 |
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
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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
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Renal coloboma syndrome
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002058130.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000156294, PMID:10587573).Stop-gained (nonsense): predicted … (more)
The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000156294, PMID:10587573).Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Gait ataxia (present) , Cataract (present) , Encephalopathy (present) , Everted lower lip vermilion (present) , Global developmental delay (present) , Large fleshy ears (present) … (more)
Gait ataxia (present) , Cataract (present) , Encephalopathy (present) , Everted lower lip vermilion (present) , Global developmental delay (present) , Large fleshy ears (present) , Long palpebral fissure (present) , Microcephaly (present) , Morning glory syndrome (present) , Nystagmus (present) , Coloboma of optic nerve (present) , Strabismus (present) , Short finger (present) , Thick eyebrow (present) , Thick lower lip vermilion (present) , Thick upper lip vermilion (present) , Tremor (present) , Seizure (present) , Intellectual disability, mild (present) (less)
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Pathogenic
(Jan 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Focal segmental glomerulosclerosis 7
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002061230.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
Thec.685C>T;p.(Arg229*) variant creates a premature translational stop signal in the PAX2 gene. It is expected to result in an absent or disrupted protein product -PVS1. … (more)
Thec.685C>T;p.(Arg229*) variant creates a premature translational stop signal in the PAX2 gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 156294; PMID: 21654726; 23539225) - PS4. This variant is not present in population databases (rs76492282, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Uruguay
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Pathogenic
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Renal coloboma syndrome
Focal segmental glomerulosclerosis 7
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
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Invitae
Accession: SCV004573223.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg229*) in the PAX2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg229*) in the PAX2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAX2 are known to be pathogenic (PMID: 11461952, 24676634, 35444690). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with PAX2-related conditions (PMID: 23539225, 34696790, 35444690). In at least one individual the variant was observed to be de novo. This variant is also known as c.754C>T (p.Arg252*). ClinVar contains an entry for this variant (Variation ID: 156294). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762007.1
First in ClinVar: Jul 30, 2021 Last updated: Jul 30, 2021 |
Clinical Features:
Proteinuria (present) , Renal dysplasia (present)
Sex: male
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Pathogenic
(Aug 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Renal coloboma syndrome
Focal segmental glomerulosclerosis 7
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002810481.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
unknown
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ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000189502.1
First in ClinVar: Oct 06, 2014 Last updated: Oct 06, 2014
Comment:
Based on information supplied by Graeme Grimes.
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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
HelpTitle | Author | Journal | Year | Link |
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Detection of De Novo PAX2 Variants and Phenotypes in Chinese Population: A Single-Center Study. | Xiong HY | Frontiers in genetics | 2022 | PMID: 35444690 |
Phenotypic spectrum and genetics of PAX2-related disorder in the Chinese cohort. | Yang X | BMC medical genomics | 2021 | PMID: 34696790 |
Mutations in PAX2 associate with adult-onset FSGS. | Barua M | Journal of the American Society of Nephrology : JASN | 2014 | PMID: 24676634 |
Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes. | Madariaga L | Clinical journal of the American Society of Nephrology : CJASN | 2013 | PMID: 23539225 |
Renal coloboma syndrome. | Schimmenti LA | European journal of human genetics : EJHG | 2011 | PMID: 21654726 |
PAX2 gene mutation in a family with isolated renal hypoplasia. | Nishimoto K | Journal of the American Society of Nephrology : JASN | 2001 | PMID: 11461952 |
Primary renal hypoplasia in humans and mice with PAX2 mutations: evidence of increased apoptosis in fetal kidneys of Pax2(1Neu) +/- mutant mice. | Porteous S | Human molecular genetics | 2000 | PMID: 10587573 |
Text-mined citations for rs76492282 ...
HelpRecord last updated Mar 05, 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.