NM_024426.6(WT1):c.73T>C (p.Ser25Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 18, 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:: RCV003788955.2

Allele description [Variation Report for NM_024426.6(WT1):c.73T>C (p.Ser25Pro)]

NM_024426.6(WT1):c.73T>C (p.Ser25Pro)

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.73T>C (p.Ser25Pro)

HGVS:

NC_000011.10:g.32435288A>G
NG_009272.1:g.5254T>C
NG_050766.1:g.4541A>G
NG_050766.2:g.5220A>G
NM_000378.6:c.73T>C
NM_001407044.1:c.73T>C
NM_001407045.1:c.73T>C
NM_001407046.1:c.73T>C
NM_001407047.1:c.73T>C
NM_001407048.1:c.73T>C
NM_001407049.1:c.73T>C
NM_001407050.1:c.73T>C
NM_024424.5:c.73T>C
NM_024425.2:c.58T>C
NM_024426.6:c.73T>CMANE SELECT
NP_000369.4:p.Ser25Pro
NP_001393973.1:p.Ser25Pro
NP_001393974.1:p.Ser25Pro
NP_001393975.1:p.Ser25Pro
NP_001393976.1:p.Ser25Pro
NP_001393977.1:p.Ser25Pro
NP_001393978.1:p.Ser25Pro
NP_001393979.1:p.Ser25Pro
NP_077742.3:p.Ser25Pro
NP_077743.2:p.Ser20Pro
NP_077744.3:p.Ser20Pro
NP_077744.4:p.Ser25Pro
LRG_525t1:c.58T>C
LRG_525:g.5254T>C
LRG_525p1:p.Ser20Pro
NC_000011.9:g.32456834A>G
NM_024426.3:c.58T>C
NR_160306.1:n.252T>C
NR_176266.1:n.252T>C

Protein change:

S20P

Molecular consequence:

NM_000378.6:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407044.1:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407045.1:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407046.1:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407047.1:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407048.1:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407049.1:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407050.1:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024425.2:c.58T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.73T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.252T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176266.1:n.252T>C - 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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Polo-like kinase 5 (Drosophila) [Mus musculus]
Polo-like kinase 5 (Drosophila) [Mus musculus]
gi|71043438|gb|AAH99679.1|

Protein
Homo sapiens splicing factor 4, mRNA (cDNA clone IMAGE:6205595), partial cds
Homo sapiens splicing factor 4, mRNA (cDNA clone IMAGE:6205595), partial cds
gi|39793919|gb|BC063784.1|

Nucleotide
Homo sapiens splicing factor 4, mRNA (cDNA clone IMAGE:2823247), partial cds
Homo sapiens splicing factor 4, mRNA (cDNA clone IMAGE:2823247), partial cds
gi|12804254|gb|BC002986.1|

Nucleotide
nsv528118 (1)
dbVar

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004572425	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 18, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004572425

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 18, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004572425.1

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

Description

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 20 of the WT1 protein (p.Ser20Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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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