NM_024426.6(WT1):c.500T>A (p.Val167Asp) AND Nephrotic syndrome, type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 24, 2020
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:: RCV001093599.1

Allele description [Variation Report for NM_024426.6(WT1):c.500T>A (p.Val167Asp)]

NM_024426.6(WT1):c.500T>A (p.Val167Asp)

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.500T>A (p.Val167Asp)

HGVS:

NC_000011.10:g.32434861A>T
NG_009272.1:g.5681T>A
NG_050766.2:g.4793A>T
NM_000378.6:c.500T>A
NM_001407044.1:c.500T>A
NM_001407045.1:c.500T>A
NM_001407046.1:c.500T>A
NM_001407047.1:c.500T>A
NM_001407048.1:c.500T>A
NM_001407049.1:c.500T>A
NM_001407050.1:c.500T>A
NM_024424.5:c.500T>A
NM_024425.2:c.485T>A
NM_024426.6:c.500T>AMANE SELECT
NP_000369.4:p.Val167Asp
NP_001393973.1:p.Val167Asp
NP_001393974.1:p.Val167Asp
NP_001393975.1:p.Val167Asp
NP_001393976.1:p.Val167Asp
NP_001393977.1:p.Val167Asp
NP_001393978.1:p.Val167Asp
NP_001393979.1:p.Val167Asp
NP_077742.3:p.Val167Asp
NP_077743.2:p.Val162Asp
NP_077744.3:p.Val162Asp
NP_077744.4:p.Val167Asp
LRG_525t1:c.485T>A
LRG_525:g.5681T>A
LRG_525p1:p.Val162Asp
NC_000011.9:g.32456407A>T
NG_050766.1:g.4114A>T
NM_024426.3:c.485T>A
NR_160306.1:n.679T>A
NR_176266.1:n.679T>A

Protein change:

V162D

Links:

dbSNP: rs1853443391

NCBI 1000 Genomes Browser:

rs1853443391

Molecular consequence:

NM_000378.6:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407044.1:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407045.1:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407046.1:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407047.1:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407048.1:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407049.1:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407050.1:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024425.2:c.485T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.500T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.679T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Nephrotic syndrome, type 4 (NPHS4)
Synonyms:: Familial mesangial sclerosis; Nephrotic syndrome, early onset with diffuse mesangial sclerosis
Identifiers:: MONDO: MONDO:0009733; MedGen: C3151568; Orphanet: 656; OMIM: 256370

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001245069	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 24, 2020)	de novo	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

SCV001245069

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 24, 2020)

de novo

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	de novo	yes	1	not provided	not provided	not provided	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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001245069.1

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

Description

A heterozygous c.485T>A (p.Val162Asp) variant in WT1 was detected in this individual. This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.485T>A (p.Val162Asp) variant, found in exon 1/10, is predicted by in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. However, low-level parental mosaicism cannot be excluded. Based on the available evidence, the c.485T>A (p.Val162Asp) variant is classified as Likely Pathogenic.

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

Last Updated: Mar 26, 2023

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