ClinVar Genomic variation as it relates to human health
NM_024426.6(WT1):c.216G>T (p.Gln72His)
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_024426.6(WT1):c.216G>T (p.Gln72His)
Variation ID: 241479 Accession: VCV000241479.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p13 11: 32435145 (GRCh38) [ NCBI UCSC ] 11: 32456691 (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 31, 2016 May 12, 2024 Apr 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024426.6:c.216G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_077744.4:p.Gln72His missense NM_000378.6:c.216G>T NP_000369.4:p.Gln72His missense NM_024424.5:c.216G>T NP_077742.3:p.Gln72His missense NR_160306.1:n.395G>T non-coding transcript variant NC_000011.10:g.32435145C>A NC_000011.9:g.32456691C>A NG_009272.1:g.5397G>T NG_050766.1:g.4398C>A LRG_525:g.5397G>T - Protein change
- Q72H
- Other names
- -
- Canonical SPDI
- NC_000011.10:32435144:C:A
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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.
The Genome Aggregation Database (gnomAD) 0.00036
Trans-Omics for Precision Medicine (TOPMed) 0.00053
The Genome Aggregation Database (gnomAD), exomes 0.00125
Exome Aggregation Consortium (ExAC) 0.00321
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 | ||
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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
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. |
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WT1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
896 | 1644 | |
LOC107982234 | - | - | - | GRCh38 | - | 725 |
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. |
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Benign (1) |
criteria provided, single submitter
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Jan 30, 2024 | RCV000232293.20 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV000239344.16 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Dec 5, 2021 | RCV000390844.14 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Dec 5, 2021 | RCV000347621.14 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Apr 1, 2024 | RCV001697685.18 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV001820765.13 | |
Benign (1) |
criteria provided, single submitter
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Dec 5, 2021 | RCV002243921.9 | |
Benign (1) |
criteria provided, single submitter
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Dec 5, 2021 | RCV002243920.9 | |
Benign (1) |
criteria provided, single submitter
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Nov 5, 2019 | RCV004547615.1 |
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
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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Likely benign
(Apr 21, 2019)
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criteria provided, single submitter
Method: clinical testing
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Nephrotic syndrome, type 4
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000371505.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 21, 2019)
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criteria provided, single submitter
Method: clinical testing
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Meacham syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000371506.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 21, 2019)
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criteria provided, single submitter
Method: clinical testing
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Wilms tumor 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000371504.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Feb 25, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000718360.2
First in ClinVar: Apr 09, 2018 Last updated: Sep 26, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 28873162, 27745835)
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Likely benign
(Sep 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Wilms tumor 1
Affected status: unknown
Allele origin:
unknown
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000297312.3
First in ClinVar: Jul 31, 2016 Last updated: Dec 24, 2022 |
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Benign
(Jan 30, 2024)
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criteria provided, single submitter
Method: clinical testing
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Wilms tumor 1
Drash syndrome 11p partial monosomy syndrome Frasier syndrome
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: SCV000290750.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
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Likely benign
(Dec 19, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002071540.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Benign
(Dec 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Drash syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002515085.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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Benign
(Dec 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Frasier syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002515087.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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Benign
(Dec 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Meacham syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002515088.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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Benign
(Dec 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Nephrotic syndrome, type 4
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002515089.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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Benign
(Dec 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Wilms tumor 1
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002515090.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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Benign
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002819497.2
First in ClinVar: Jan 15, 2023 Last updated: Jun 03, 2023 |
Comment:
Variant summary: WT1 c.216G>T (p.Gln72His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign … (more)
Variant summary: WT1 c.216G>T (p.Gln72His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 117694 control chromosomes. The observed variant frequency is approximately 133 fold of the estimated maximal expected allele frequency for a pathogenic variant in WT1 causing Wilms Tumor, Type 1 phenotype (9.4e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.216G>T in individuals affected with Wilms Tumor, Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Wilms tumor 1
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016266.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(Nov 05, 2019)
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criteria provided, single submitter
Method: clinical testing
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WT1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004755544.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Benign
(Apr 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002544557.11
First in ClinVar: Jul 09, 2022 Last updated: May 12, 2024 |
Comment:
WT1: BS1, BS2
Number of individuals with the variant: 12
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs5030135 ...
HelpRecord last updated May 19, 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.