NM_024494.3(WNT2B):c.205C>T (p.Arg69Ter) AND Diarrhea 9

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 31, 2018
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000714963.1

Allele description [Variation Report for NM_024494.3(WNT2B):c.205C>T (p.Arg69Ter)]

NM_024494.3(WNT2B):c.205C>T (p.Arg69Ter)

Gene:

WNT2B:Wnt family member 2B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p13.2

Genomic location:

Preferred name:

NM_024494.3(WNT2B):c.205C>T (p.Arg69Ter)

HGVS:

NC_000001.11:g.112514896C>T
NG_052953.1:g.53356C>T
NM_001291880.1:c.-72C>T
NM_004185.4:c.148C>T
NM_024494.3:c.205C>TMANE SELECT
NP_004176.2:p.Arg50Ter
NP_078613.1:p.Arg69Ter
NC_000001.10:g.113057518C>T
NM_024494.2:c.205C>T

Protein change:

R50*; ARG69TER

Links:

OMIM: 601968.0001; dbSNP: rs370244148

NCBI 1000 Genomes Browser:

rs370244148

Molecular consequence:

NM_001291880.1:c.-72C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_004185.4:c.148C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_024494.3:c.205C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Diarrhea 9
Identifiers:: MONDO: MONDO:0032575; MedGen: C4748517; OMIM: 618168

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000845728	OMIM	no assertion criteria provided	Pathogenic (Oct 31, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000845728

OMIM

no assertion criteria provided

Pathogenic
(Oct 31, 2018)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations.

O'Connell AE, Zhou F, Shah MS, Murphy Q, Rickner H, Kelsen J, Boyle J, Doyle JJ, Gangwani B, Thiagarajah JR, Kamin DS, Goldsmith JD, Richmond C, Breault DT, Agrawal PB.

Am J Hum Genet. 2018 Jul 5;103(1):131-137. doi: 10.1016/j.ajhg.2018.05.007. Epub 2018 Jun 14.

PubMed [citation]

PMID:: 29909964
PMCID:: PMC6035368

Details of each submission

From OMIM, SCV000845728.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a Kuwaiti brother and sister with neonatal-onset chronic diarrhea (DIAR9; 618168), O'Connell et al. (2018) identified homozygosity for a c.205C-T transition (c.205C-T, NM_024494) in the WNT2B gene, resulting in an arg69-to-ter (R69X) substitution. Their unaffected parents and 3 unaffected sibs were heterozygous for the mutation, which was detected in heterozygous state 3 times in the gnomAD database and 1 time in the ExAC database. Immunofluorescence showed diminished staining for OLFM4 (614061), a marker for intestinal stem cells, and enteroid cultures generated from patient intestinal epithelium could not be expanded and did not survive passage. Quantitative RT-PCR of patient enteroids showed a 10-fold increase in LEF1 (153245) mRNA and a 100-fold reduction in TLR4 (603030) expression compared to controls, indicating alterations in canonical WNT and microbial pattern-recognition signaling.

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

Last Updated: Apr 23, 2022

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