NM_024426.6(WT1):c.1447+5G>A AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 13, 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:: RCV000705142.8

Allele description [Variation Report for NM_024426.6(WT1):c.1447+5G>A]

NM_024426.6(WT1):c.1447+5G>A

Gene:

WT1:WT1 transcription factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p13

Genomic location:

Preferred name:

NM_024426.6(WT1):c.1447+5G>A

Other names:

splice site; 1432+5G>A; IVS9+5G>A

HGVS:

NC_000011.10:g.32391967C>T
NG_009272.1:g.48575G>A
NM_000378.6:c.1387+14G>A
NM_001198551.2:c.787+14G>A
NM_001198552.2:c.745+5G>A
NM_001367854.1:c.259+5G>A
NM_001407044.1:c.1432+14G>A
NM_001407045.1:c.1396+5G>A
NM_001407046.1:c.1354+699G>A
NM_001407047.1:c.1315+14G>A
NM_001407048.1:c.1306+5G>A
NM_001407049.1:c.1303+699G>A
NM_001407050.1:c.1273+5G>A
NM_001407051.1:c.685+5G>A
NM_024424.5:c.1438+14G>A
NM_024426.6:c.1447+5G>AMANE SELECT
LRG_525:g.48575G>A
NC_000011.9:g.32413513C>T
NM_024426.2:c.1228+5G>A
NM_024426.4:c.1432+5G>A

Nucleotide change:

IVS9DS, G-A, +5

Links:

OMIM: 607102.0009; OMIM: 607102.0020; dbSNP: rs587776576

NCBI 1000 Genomes Browser:

rs587776576

Molecular consequence:

NM_000378.6:c.1387+14G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001198551.2:c.787+14G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001198552.2:c.745+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001367854.1:c.259+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407044.1:c.1432+14G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407045.1:c.1396+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407046.1:c.1354+699G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407047.1:c.1315+14G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407048.1:c.1306+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407049.1:c.1303+699G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407050.1:c.1273+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407051.1:c.685+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_024424.5:c.1438+14G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_024426.6:c.1447+5G>A - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000834127	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 13, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 17576681, 9536098, 1302008, 9499425, 20442690, 25818337, 27719739, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000834127

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 13, 2023)

germline

clinical testing

PubMed (8)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000834127.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in the activation of a cryptic splice site in intron 9 (PMID: 1302008, 9499425). ClinVar contains an entry for this variant (Variation ID: 3493). This variant is also known as IVS9+5G>A and c.1228+5G>A. This variant has been observed in individual(s) with Frasier syndrome and/or steroid-resistant nephrotic syndrome (PMID: 9499425, 20442690, 25818337, 27719739). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 9 of the WT1 gene. It does not directly change the encoded amino acid sequence of the WT1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame.

#	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: Nov 3, 2024

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