U.S. flag

An official website of the United States government

NM_024426.6(WT1):c.1447+4C>T AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 3, 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:
RCV001216104.7

Allele description [Variation Report for NM_024426.6(WT1):c.1447+4C>T]

NM_024426.6(WT1):c.1447+4C>T

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+4C>T
Other names:
1432+4C>T; IVS9+4C>T
HGVS:
  • NC_000011.10:g.32391968G>A
  • NG_009272.1:g.48574C>T
  • NM_000378.6:c.1387+13C>T
  • NM_001198551.2:c.787+13C>T
  • NM_001198552.2:c.745+4C>T
  • NM_001367854.1:c.259+4C>T
  • NM_001407044.1:c.1432+13C>T
  • NM_001407045.1:c.1396+4C>T
  • NM_001407046.1:c.1354+698C>T
  • NM_001407047.1:c.1315+13C>T
  • NM_001407048.1:c.1306+4C>T
  • NM_001407049.1:c.1303+698C>T
  • NM_001407050.1:c.1273+4C>T
  • NM_001407051.1:c.685+4C>T
  • NM_024424.5:c.1438+13C>T
  • NM_024426.6:c.1447+4C>TMANE SELECT
  • LRG_525:g.48574C>T
  • NC_000011.9:g.32413514G>A
  • NM_024426.4:c.1432+4C>T
Nucleotide change:
IVS9DS, C-T, +4
Links:
OMIM: 607102.0018; dbSNP: rs587776577
NCBI 1000 Genomes Browser:
rs587776577
Molecular consequence:
  • NM_000378.6:c.1387+13C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001198551.2:c.787+13C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001198552.2:c.745+4C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367854.1:c.259+4C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407044.1:c.1432+13C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407045.1:c.1396+4C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407046.1:c.1354+698C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407047.1:c.1315+13C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407048.1:c.1306+4C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407049.1:c.1303+698C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407050.1:c.1273+4C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407051.1:c.685+4C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_024424.5:c.1438+13C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_024426.6:c.1447+4C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Drash syndrome (DDS)
Synonyms:
NEPHROPATHY, WILMS TUMOR, AND GENITAL ANOMALIES; WILMS TUMOR AND PSEUDO- OR TRUE HERMAPHRODITISM; Wilms tumor and pseudohermaphroditism; 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001387881Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Feb 3, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.

Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, Gessler M.

Hum Mol Genet. 1998 Apr;7(4):709-14.

PubMed [citation]
PMID:
9499425

Long-term outcomes and molecular analysis of a large cohort of patients with 46,XY disorder of sex development due to partial gonadal dysgenesis.

Gomes NL, Lerário AM, Machado AZ, Moraes DR, Silva TED, Arnhold IJP, Batista RL, Faria Júnior JAD, Costa EF, Nishi MY, Inacio M, Domenice S, Mendonca BB.

Clin Endocrinol (Oxf). 2018 Aug;89(2):164-177. doi: 10.1111/cen.13717. Epub 2018 May 23.

PubMed [citation]
PMID:
29668062
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001387881.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

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. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with WT1-related disorders (PMID: 9398852, 9499425, 29668062). In at least one individual the variant was observed to be de novo. This variant is also known as IVS9+4C>T. ClinVar contains an entry for this variant (Variation ID: 3500). 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 exon 9 (PMID: 9398852, 12050205). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 13, 2025