NM_024426.6(WT1):c.196del (p.Ala66fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 4, 2023
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:: RCV003812278.2

Allele description [Variation Report for NM_024426.6(WT1):c.196del (p.Ala66fs)]

NM_024426.6(WT1):c.196del (p.Ala66fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

11p13

Genomic location:

Preferred name:

NM_024426.6(WT1):c.196del (p.Ala66fs)

HGVS:

NC_000011.10:g.32435168del
NG_009272.1:g.5377del
NG_050766.1:g.4421del
NG_050766.2:g.5100del
NM_000378.6:c.196del
NM_001407044.1:c.196del
NM_001407045.1:c.196del
NM_001407046.1:c.196del
NM_001407047.1:c.196del
NM_001407048.1:c.196del
NM_001407049.1:c.196del
NM_001407050.1:c.196del
NM_024424.5:c.196del
NM_024425.2:c.178delG
NM_024426.6:c.196delMANE SELECT
NP_000369.4:p.Ala66fs
NP_001393973.1:p.Ala66fs
NP_001393974.1:p.Ala66fs
NP_001393975.1:p.Ala66fs
NP_001393976.1:p.Ala66fs
NP_001393977.1:p.Ala66fs
NP_001393978.1:p.Ala66fs
NP_001393979.1:p.Ala66fs
NP_077742.3:p.Ala66fs
NP_077743.2:p.Ala61Argfs
NP_077744.3:p.Ala61Argfs
NP_077744.4:p.Ala66fs
LRG_525t1:c.178del
LRG_525:g.5377del
LRG_525p1:p.Ala61Argfs
NC_000011.9:g.32456711del
NC_000011.9:g.32456714del
NM_024426.3:c.178delG
NR_160306.1:n.375del
NR_176266.1:n.375del

Protein change:

A66fs

Molecular consequence:

NM_000378.6:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407044.1:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407045.1:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407046.1:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407047.1:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407048.1:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407049.1:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407050.1:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024424.5:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024425.2:c.178delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024426.6:c.196del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_160306.1:n.375del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176266.1:n.375del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

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uncharacterized protein An02g12040 [Aspergillus niger]
uncharacterized protein An02g12040 [Aspergillus niger]
gi|145233919|ref|XP_001400332.1|

Protein
centrobin isoform X4 [Homo sapiens]
centrobin isoform X4 [Homo sapiens]
gi|2217309832|ref|XP_047291260.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004606994	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 4, 2023)	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

SCV004606994

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 4, 2023)

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, SCV004606994.1

#	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 affected with WT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala61Argfs*16) in the WT1 gene. It is unclear whether it will result in an absent or disrupted protein product because a major initiation site located at codon 69 has the potential to rescue this variant.

#	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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