NM_024426.6(WT1):c.1218A>C (p.Arg406Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 23, 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:: RCV000653799.10

Allele description [Variation Report for NM_024426.6(WT1):c.1218A>C (p.Arg406Ser)]

NM_024426.6(WT1):c.1218A>C (p.Arg406Ser)

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.1218A>C (p.Arg406Ser)

HGVS:

NC_000011.10:g.32396303T>G
NG_009272.1:g.44239A>C
NM_000378.6:c.1167A>C
NM_001198551.2:c.567A>C
NM_001198552.2:c.516A>C
NM_001367854.1:c.30A>C
NM_001407044.1:c.1212A>C
NM_001407045.1:c.1167A>C
NM_001407046.1:c.1218A>C
NM_001407047.1:c.1095A>C
NM_001407048.1:c.1167A>C
NM_001407049.1:c.1167A>C
NM_001407050.1:c.1044A>C
NM_001407051.1:c.456A>C
NM_024424.5:c.1218A>C
NM_024425.2:c.1152A>C
NM_024426.6:c.1218A>CMANE SELECT
NP_000369.4:p.Arg389Ser
NP_001185480.1:p.Arg189Ser
NP_001185480.1:p.Arg189Ser
NP_001185481.1:p.Arg172Ser
NP_001354783.1:p.Arg10Ser
NP_001393973.1:p.Arg404Ser
NP_001393974.1:p.Arg389Ser
NP_001393975.1:p.Arg406Ser
NP_001393976.1:p.Arg365Ser
NP_001393977.1:p.Arg389Ser
NP_001393978.1:p.Arg389Ser
NP_001393979.1:p.Arg348Ser
NP_001393980.1:p.Arg152Ser
NP_077742.3:p.Arg406Ser
NP_077743.2:p.Arg384Ser
NP_077744.3:p.Arg401Ser
NP_077744.4:p.Arg406Ser
LRG_525t1:c.1203A>C
LRG_525t2:c.567A>C
LRG_525:g.44239A>C
LRG_525p1:p.Arg401Ser
LRG_525p2:p.Arg189Ser
NC_000011.9:g.32417849T>G
NM_001198551.1:c.567A>C
NM_024426.3:c.1203A>C
NM_024426.4:c.1203A>C
NR_160306.1:n.1550A>C
NR_176266.1:n.1499A>C

Protein change:

R10S

Links:

dbSNP: rs1554939793

NCBI 1000 Genomes Browser:

rs1554939793

Molecular consequence:

NM_000378.6:c.1167A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001198551.2:c.567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001198552.2:c.516A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001367854.1:c.30A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407044.1:c.1212A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407045.1:c.1167A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407046.1:c.1218A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407047.1:c.1095A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407048.1:c.1167A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407049.1:c.1167A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407050.1:c.1044A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407051.1:c.456A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.1218A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024425.2:c.1152A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.1218A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.1550A>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

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Arabidopsis thaliana Core-2/I-branching beta-1,6-N-acetylglucosaminyltransferase...
Arabidopsis thaliana Core-2/I-branching beta-1,6-N-acetylglucosaminyltransferase family protein (AT3G21310), mRNA
gi|1063712919|ref|NM_001338526.1|

Nucleotide
Homo sapiens BAC clone CH17-254B7 from chromosome 1, complete sequence
Homo sapiens BAC clone CH17-254B7 from chromosome 1, complete sequence
gi|307746952|gb|AC242498.3||gnl|wug 17-254B7

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000775689	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 23, 2019)	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

SCV000775689

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 23, 2019)

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, SCV000775689.6

#	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 arginine with serine at codon 401 of the WT1 protein (p.Arg401Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 543136). This variant is not present in population databases (ExAC no frequency).

#	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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