NM_024426.6(WT1):c.162C>G (p.Ser54Arg) AND Wilms tumor 1

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Dec 13, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000709153.8

Allele description [Variation Report for NM_024426.6(WT1):c.162C>G (p.Ser54Arg)]

NM_024426.6(WT1):c.162C>G (p.Ser54Arg)

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.162C>G (p.Ser54Arg)

HGVS:

NC_000011.10:g.32435199G>C
NG_009272.1:g.5343C>G
NG_050766.1:g.4452G>C
NM_000378.6:c.162C>G
NM_024424.5:c.162C>G
NM_024426.6:c.162C>GMANE SELECT
NP_000369.4:p.Ser54Arg
NP_077742.3:p.Ser54Arg
NP_077744.4:p.Ser54Arg
LRG_525:g.5343C>G
NC_000011.9:g.32456745G>C
NM_024426.4:c.147C>G
NR_160306.1:n.341C>G

Protein change:

S54R

Links:

dbSNP: rs776954184

NCBI 1000 Genomes Browser:

rs776954184

Molecular consequence:

NM_000378.6:c.162C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.162C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.162C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.341C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Wilms tumor 1 (WT1)
Synonyms:: Wilms tumor, somatic
Identifiers:: MONDO: MONDO:0008679; MedGen: CN033288; Orphanet: 654; OMIM: 194070

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000371520	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV000838444	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV004821687	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Dec 13, 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

SCV000371520

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV000838444

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(Jul 2, 2018)

unknown

clinical testing

Citation Link,

SCV004821687

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Dec 13, 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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	12	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000371520.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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

From Mendelics, SCV000838444.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From All of Us Research Program, National Institutes of Health, SCV004821687.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	12	not provided	not provided	clinical testing	PubMed (1)

Description

This variant is located in the WT1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with WT1-related disorders in the literature. This variant has been identified in 5/160972 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		12	not provided	not provided	not provided

Last Updated: Jun 9, 2024

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