NM_024426.6(WT1):c.1316G>A (p.Arg439His) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 8, 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:: RCV001250546.2

Allele description [Variation Report for NM_024426.6(WT1):c.1316G>A (p.Arg439His)]

NM_024426.6(WT1):c.1316G>A (p.Arg439His)

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.1316G>A (p.Arg439His)

Other names:

R366H

HGVS:

NC_000011.10:g.32392704C>T
NG_009272.1:g.47838G>A
NM_000378.6:c.1265G>A
NM_001198551.2:c.665G>A
NM_001198552.2:c.614G>A
NM_001367854.1:c.128G>A
NM_001407044.1:c.1310G>A
NM_001407045.1:c.1265G>A
NM_001407046.1:c.1316G>A
NM_001407047.1:c.1193G>A
NM_001407049.1:c.1265G>A
NM_001407050.1:c.1142G>A
NM_001407051.1:c.554G>A
NM_024424.5:c.1316G>A
NM_024425.2:c.1250G>A
NM_024426.6:c.1316G>AMANE SELECT
NP_000369.4:p.Arg422His
NP_001185480.1:p.Arg222His
NP_001185480.1:p.Arg222His
NP_001185481.1:p.Arg205His
NP_001354783.1:p.Arg43His
NP_001393973.1:p.Arg437His
NP_001393974.1:p.Arg422His
NP_001393975.1:p.Arg439His
NP_001393976.1:p.Arg398His
NP_001393978.1:p.Arg422His
NP_001393979.1:p.Arg381His
NP_001393980.1:p.Arg185His
NP_077742.3:p.Arg439His
NP_077743.2:p.Arg417His
NP_077744.3:p.Arg434His
NP_077744.4:p.Arg439His
LRG_525t1:c.1301G>A
LRG_525t2:c.665G>A
LRG_525:g.47838G>A
LRG_525p1:p.Arg434His
LRG_525p2:p.Arg222His
NC_000011.9:g.32414250C>T
NM_001198551.1:c.665G>A
NM_024426.2:c.1097G>A
NM_024426.3:c.1301G>A
NM_024426.4:c.1301G>A
NM_024426.5:c.1316G>A
NR_160306.1:n.1648G>A
NR_176266.1:n.1597G>A

Protein change:

R185H; ARG366HIS

Links:

OMIM: 607102.0004; dbSNP: rs121907901

NCBI 1000 Genomes Browser:

rs121907901

Molecular consequence:

NM_000378.6:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001198551.2:c.665G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001198552.2:c.614G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001367854.1:c.128G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407044.1:c.1310G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407045.1:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407046.1:c.1316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407047.1:c.1193G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407049.1:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407050.1:c.1142G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407051.1:c.554G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.1316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024425.2:c.1250G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.1316G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.1648G>A - 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:: 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

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
SCV001425363	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 8, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 27300205, 27719739, 30963316, 31937884, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001425363

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 8, 2020)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Genotype-phenotype analysis of pediatric patients with WT1 glomerulopathy.

Ahn YH, Park EJ, Kang HG, Kim SH, Cho HY, Shin JI, Lee JH, Park YS, Kim KS, Ha IS, Cheong HI.

Pediatr Nephrol. 2017 Jan;32(1):81-89. Epub 2016 Jun 14.

PubMed [citation]

PMID:: 27300205

Early recognition of gonadal dysgenesis in congenital nephrotic syndrome .

Ukarapong S, Berkovitz G, McElreavey K, Bashamboo A, Bao Y.

Clin Nephrol. 2016 Dec;86 (2016)(12):341-344.

PubMed [citation]

PMID:: 27719739

See all PubMed Citations (5)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV001425363.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This WT1 variant has been reported in multiple individuals presenting with congenital nephrotic syndrome. A functional study has demonstrated that this variant is associated with a decrease in DNA binding affinity when compared to the wild-type protein. WT1 c.1301G>A is located within one of the four zinc finger regions that are important for protein function. This variant is absent from a large population dataset and has been reported in ClinVar. Three bioinformatic tools queried predict that this substitution would be damaging, and the arginine residue at this position is highly evolutionarily conserved across all species assessed. We consider this variant to be pathogenic.

#	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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Relating variation to medicine