NM_024426.6(WT1):c.87C>A (p.Cys29Ter) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 13, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001214489.8

Allele description [Variation Report for NM_024426.6(WT1):c.87C>A (p.Cys29Ter)]

NM_024426.6(WT1):c.87C>A (p.Cys29Ter)

Genes:

WT1:WT1 transcription factor [Gene - OMIM - HGNC]
LOC107982234:WT1/WT1-AS bi-directional promoter region [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

11p13

Genomic location:

Preferred name:

NM_024426.6(WT1):c.87C>A (p.Cys29Ter)

HGVS:

NC_000011.10:g.32435274G>T
NG_009272.1:g.5268C>A
NG_050766.1:g.4527G>T
NM_000378.6:c.87C>A
NM_024424.5:c.87C>A
NM_024426.6:c.87C>AMANE SELECT
NP_000369.4:p.Cys29Ter
NP_077742.3:p.Cys29Ter
NP_077744.4:p.Cys29Ter
LRG_525:g.5268C>A
NC_000011.9:g.32456820G>T
NM_024426.4:c.72C>A
NR_160306.1:n.266C>A

Protein change:

C29*

Links:

dbSNP: rs1554946770

NCBI 1000 Genomes Browser:

rs1554946770

Molecular consequence:

NR_160306.1:n.266C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000378.6:c.87C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_024424.5:c.87C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_024426.6:c.87C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Drash syndrome (DDS)
Synonyms:: WILMS TUMOR AND PSEUDO- OR TRUE HERMAPHRODITISM; Wilms tumor and pseudohermaphroditism; Nephropathy, wilms tumor, and genital anomalies; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008682; MedGen: C0950121; Orphanet: 220; OMIM: 194080

Name:: Frasier syndrome
Identifiers:: MONDO: MONDO:0007635; MeSH: D052159; MedGen: C0950122; Orphanet: 347; OMIM: 136680

Name:: Wilms tumor 1 (WT1)
Synonyms:: Wilms tumor, somatic
Identifiers:: MONDO: MONDO:0008679; MedGen: CN033288; Orphanet: 654; OMIM: 194070

Name:: 11p partial monosomy syndrome (WAGR)
Synonyms:: CHROMOSOME 11p13 DELETION SYNDROME; WAGR syndrome; WAGR Complex; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008681; MedGen: C0206115; Orphanet: 893; OMIM: 194072

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001386172	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 13, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 28811308, 16987884, 8621495, 12640141, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001386172

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 13, 2019)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Wilms' tumour 1 (WT1) in development, homeostasis and disease.

Hastie ND.

Development. 2017 Aug 15;144(16):2862-2872. doi: 10.1242/dev.153163. Review.

PubMed [citation]

PMID:: 28811308

The many facets of the Wilms' tumour gene, WT1.

Hohenstein P, Hastie ND.

Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R196-201. Review.

PubMed [citation]

PMID:: 16987884

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001386172.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Downstream of the non-canonical translation start site (CTG) at codon 1, the nearest methionine codon that can be used to initiate translation of the WT1 protein lies at codon 69. This downstream in-frame ATG is known as a major initiation site (PMID: 28811308, 16987884, 8621495). The functional significance of the different WT1 protein isoforms is unknown (PMID: 8621495), however mice lacking the N-terminal 68 amino acids develop normally and are fertile (PMID: 12640141). Based on these results, the impact of this variant on WT1 protein function is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with WT1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change results in a premature translational stop signal in the WT1 gene (p.Cys24*). It is unclear whether it will result in an absent or disrupted protein product because a highly conserved, in-frame methionine located at codon 69 has the potential to rescue protein translation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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