NM_001370466.1(NOD2):c.2717+158C>T AND Autoinflammatory syndrome

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Nov 5, 2019
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:: RCV001029749.14

Allele description [Variation Report for NM_001370466.1(NOD2):c.2717+158C>T]

NM_001370466.1(NOD2):c.2717+158C>T

Gene:

NOD2:nucleotide binding oligomerization domain containing 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_001370466.1(NOD2):c.2717+158C>T

HGVS:

NC_000016.10:g.50722863C>T
NG_007508.1:g.30725C>T
NM_001293557.2:c.2717+158C>T
NM_001370466.1:c.2717+158C>TMANE SELECT
NM_022162.3:c.2798+158C>T
LRG_177:g.30725C>T
NC_000016.9:g.50756774C>T
NM_022162.2:c.2798+158C>T

Links:

OMIM: 605956.0007; dbSNP: rs5743289

NCBI 1000 Genomes Browser:

rs5743289

Molecular consequence:

NM_001293557.2:c.2717+158C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001370466.1:c.2717+158C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_022162.3:c.2798+158C>T - intron variant - [Sequence Ontology: SO:0001627]

Functional consequence:

no known functional consequence

Observations:

Condition(s)

Name:: Autoinflammatory syndrome
Identifiers:: MONDO: MONDO:0019751; MedGen: C3890737

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001190343	Breda Genetics srl	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Nov 5, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002542713	Genome Diagnostics Laboratory, The Hospital for Sick Children	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Dec 12, 2016)	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

SCV001190343

Breda Genetics srl

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Nov 5, 2019)

unknown

clinical testing

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

SCV002542713

Genome Diagnostics Laboratory, The Hospital for Sick Children

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Dec 12, 2016)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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 Breda Genetics srl, SCV001190343.2

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

Description

The variant is reported as risk factor for susceptibility to Crohn disease and susceptibility to Yao syndrome in ClinVar (Variation ID: 4697). It is also reported in ClinVar as pathogenic for Blau syndrome in one study for a patient with early-onset sarcoidosis and gastrointestinal granulomas (Borzutzky et al., 2010, PMID: 19467619), although in the article the authors define the variant only as polymorphism related to a susceptibility to Crohn disease. Furthermore, the variant is reported with an estimated allele frequency of 0.052 in 1000 Genomes Project and 0.1018 in gnomAD genomes, with homozygous individuals reported. We have also observed this variant in a large subset of samples without autoinflammatory syndromes at Breda Genetics. Based on the current evidence and high allele frequency, we interpret this variant as likely neutral in regard of pure mendelian inheritance for any form of genetic autoinflammatory syndrome.

#	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		1	not provided	not provided	not provided

From Genome Diagnostics Laboratory, The Hospital for Sick Children, SCV002542713.1

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

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

Last Updated: Apr 20, 2025

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