ClinVar Genomic variation as it relates to human health
NM_024426.6(WT1):c.1122A>G (p.Arg374=)
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.1122A>G (p.Arg374=)
Variation ID: 198591 Accession: VCV000198591.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p13 11: 32396399 (GRCh38) [ NCBI UCSC ] 11: 32417945 (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 2, 2016 Jul 23, 2024 Jul 15, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024426.6:c.1122A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_077744.4:p.Arg374= synonymous NM_000378.6:c.1071A>G NP_000369.4:p.Arg357= synonymous NM_001198551.2:c.471A>G NP_001185480.1:p.Arg157= synonymous NM_001198552.2:c.420A>G NP_001185481.1:p.Arg140= synonymous NM_001367854.1:c.-67A>G 5 prime UTR NM_001407044.1:c.1116A>G NP_001393973.1:p.Arg372= synonymous NM_001407045.1:c.1071A>G NP_001393974.1:p.Arg357= synonymous NM_001407046.1:c.1122A>G NP_001393975.1:p.Arg374= synonymous NM_001407047.1:c.999A>G NP_001393976.1:p.Arg333= synonymous NM_001407048.1:c.1071A>G NP_001393977.1:p.Arg357= synonymous NM_001407049.1:c.1071A>G NP_001393978.1:p.Arg357= synonymous NM_001407050.1:c.948A>G NP_001393979.1:p.Arg316= synonymous NM_001407051.1:c.360A>G NP_001393980.1:p.Arg120= synonymous NM_024424.5:c.1122A>G NP_077742.3:p.Arg374= synonymous NM_024425.2:c.1056A>G NP_077743.2:p.Arg352= synonymous NR_160306.1:n.1454A>G non-coding transcript variant NR_176266.1:n.1403A>G non-coding transcript variant NC_000011.10:g.32396399T>C NC_000011.9:g.32417945T>C NG_009272.1:g.44143A>G LRG_525:g.44143A>G LRG_525t1:c.1107A>G LRG_525p1:p.Arg369= LRG_525t2:c.471A>G LRG_525p2:p.Arg157= - Protein change
- Other names
- -
- Canonical SPDI
- NC_000011.10:32396398:T:C
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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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0.33147 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.13029
The Genome Aggregation Database (gnomAD) 0.16617
Trans-Omics for Precision Medicine (TOPMed) 0.18770
Exome Aggregation Consortium (ExAC) 0.23346
The Genome Aggregation Database (gnomAD), exomes 0.24341
1000 Genomes Project 30x 0.32167
1000 Genomes Project 0.33147
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
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. |
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WT1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
909 | 1664 |
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 (6) |
criteria provided, multiple submitters, no conflicts
|
Jul 15, 2024 | RCV000179975.14 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 5, 2021 | RCV000274499.7 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV000374772.8 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 5, 2021 | RCV000282487.7 | |
Benign (1) |
criteria provided, single submitter
|
Apr 14, 2017 | RCV000576342.3 | |
Benign (1) |
criteria provided, single submitter
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Aug 30, 2016 | RCV000587032.2 | |
Benign (1) |
criteria provided, single submitter
|
Feb 1, 2024 | RCV001516885.7 | |
Benign (1) |
criteria provided, single submitter
|
Dec 5, 2021 | RCV002243866.2 | |
Benign (1) |
criteria provided, single submitter
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Dec 5, 2021 | RCV002243867.2 | |
Benign (1) |
criteria provided, single submitter
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Mar 28, 2019 | RCV003588590.1 |
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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Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000314308.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Apr 14, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Frasier syndrome
Wilms tumor 1 Drash syndrome Nephrotic syndrome, type 4
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000677587.1
First in ClinVar: Jan 07, 2018 Last updated: Jan 07, 2018 |
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Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Nephrotic syndrome, type 4
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000371435.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Meacham syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000371432.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Wilms tumor 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000371434.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
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
|
Invitae
Accession: SCV001725249.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024 |
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Benign
(Aug 30, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699502.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The WT1 c.1107A>G (p.Arg369Arg) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a … (more)
Variant summary: The WT1 c.1107A>G (p.Arg369Arg) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 28265/121072 control chromosomes (4959 homozygotes) at a frequency of 0.2334561, which is approximately 24902 times the estimated maximal expected allele frequency of a pathogenic WT1 variant (0.0000094), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign. (less)
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Benign
(Mar 03, 2016)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000518966.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(May 21, 2015)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000232302.5
First in ClinVar: Jun 28, 2015 Last updated: Mar 08, 2017 |
Sex: mixed
|
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Benign
(Dec 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Frasier syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002515036.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
|
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Benign
(Dec 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Nephrotic syndrome, type 4
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002515038.1
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
|
Genome-Nilou Lab
Accession: SCV002515037.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
|
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Benign
(Dec 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Drash syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002515035.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
|
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Benign
(Dec 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Wilms tumor 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002515039.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
|
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Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Wilms tumor 1
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016260.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
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Benign
(Mar 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Nephroblastoma
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004360956.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
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Benign
(Jul 15, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Accession: SCV005087636.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied in a panel designed for … (more)
This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 45. Only high quality variants are reported. (less)
Number of individuals with the variant: 45
Age: <18 years
Sex: mixed
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931806.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001975964.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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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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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=WT1 | - | - | - | - |
Text-mined citations for rs16754 ...
HelpRecord last updated Jul 29, 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.