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NM_024426.6(WT1):c.1447+2T>C AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 16, 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:
RCV001218361.8

Allele description [Variation Report for NM_024426.6(WT1):c.1447+2T>C]

NM_024426.6(WT1):c.1447+2T>C

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+2T>C
HGVS:
  • NC_000011.10:g.32391970A>G
  • NG_009272.1:g.48572T>C
  • NM_000378.6:c.1387+11T>C
  • NM_001198551.2:c.787+11T>C
  • NM_001198552.2:c.745+2T>C
  • NM_001367854.1:c.259+2T>C
  • NM_001407044.1:c.1432+11T>C
  • NM_001407045.1:c.1396+2T>C
  • NM_001407046.1:c.1354+696T>C
  • NM_001407047.1:c.1315+11T>C
  • NM_001407048.1:c.1306+2T>C
  • NM_001407049.1:c.1303+696T>C
  • NM_001407050.1:c.1273+2T>C
  • NM_001407051.1:c.685+2T>C
  • NM_024424.5:c.1438+11T>C
  • NM_024426.6:c.1447+2T>CMANE SELECT
  • LRG_525:g.48572T>C
  • NC_000011.9:g.32413516A>G
  • NM_024426.4:c.1432+2T>C
Links:
dbSNP: rs1851829439
NCBI 1000 Genomes Browser:
rs1851829439
Molecular consequence:
  • NM_000378.6:c.1387+11T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001198551.2:c.787+11T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407044.1:c.1432+11T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407046.1:c.1354+696T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407047.1:c.1315+11T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407049.1:c.1303+696T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_024424.5:c.1438+11T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001198552.2:c.745+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001367854.1:c.259+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407045.1:c.1396+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407048.1:c.1306+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407050.1:c.1273+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407051.1:c.685+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_024426.6:c.1447+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001390241Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 16, 2019) 		germlineclinical testing

PubMed (5)
[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

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001390241.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID:9475094). Disruption of this splice site has been observed in individuals affected with clinical features of WT1-related disorders (PMID: 9475094, 16717397, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in the last intron (intron 9) of the WT1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

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

Last Updated: Sep 29, 2024