NM_000628.5(IL10RB):c.298T>G (p.Trp100Gly) AND Inflammatory bowel disease 25

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 4, 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:: RCV001330006.6

Allele description [Variation Report for NM_000628.5(IL10RB):c.298T>G (p.Trp100Gly)]

NM_000628.5(IL10RB):c.298T>G (p.Trp100Gly)

Genes:

IFNAR2-IL10RB:IFNAR2-IL10RB readthrough [Gene]
IL10RB:interleukin 10 receptor subunit beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.11

Genomic location:

Preferred name:

NM_000628.5(IL10RB):c.298T>G (p.Trp100Gly)

HGVS:

NC_000021.9:g.33276720T>G
NG_012089.1:g.15354T>G
NM_000628.5:c.298T>GMANE SELECT
NP_000619.3:p.Trp100Gly
LRG_152:g.15354T>G
NC_000021.8:g.34649025T>G
NM_000628.4:c.298T>G

Protein change:

W100G

Links:

dbSNP: rs868604197

NCBI 1000 Genomes Browser:

rs868604197

Molecular consequence:

NM_000628.5:c.298T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inflammatory bowel disease 25
Synonyms:: Inflammatory bowel disease 25, autosomal recessive; Inflammatory bowel disease 25, early onset, autosomal recessive
Identifiers:: MONDO: MONDO:0012941; MedGen: C2675508; Orphanet: 238569; OMIM: 612567

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001521592	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 9, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002201974	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24216686, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001521592

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 9, 2020)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002201974

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 4, 2023)

germline

clinical testing

PubMed (2)
[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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	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

Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group.

Pigneur B, Escher J, Elawad M, Lima R, Buderus S, Kierkus J, Guariso G, Canioni D, Lambot K, Talbotec C, Shah N, Begue B, Rieux-Laucat F, Goulet O, Cerf-Bensussan N, Neven B, Ruemmele FM.

Inflamm Bowel Dis. 2013 Dec;19(13):2820-8. doi: 10.1097/01.MIB.0000435439.22484.d3.

PubMed [citation]

PMID:: 24216686

See all PubMed Citations (3)

Details of each submission

From Baylor Genetics, SCV001521592.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Invitae, SCV002201974.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 100 of the IL10RB protein (p.Trp100Gly). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with very early-onset inflammatory bowel disease (PMID: 24216686). ClinVar contains an entry for this variant (Variation ID: 1028849). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IL10RB protein function. 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.

#	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: Feb 20, 2024

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