NM_001370466.1(NOD2):c.2974C>T (p.Arg992Ter) AND Blau syndrome

Germline classification:: Uncertain significance (2 submissions)
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:: RCV000084131.3

Allele description [Variation Report for NM_001370466.1(NOD2):c.2974C>T (p.Arg992Ter)]

NM_001370466.1(NOD2):c.2974C>T (p.Arg992Ter)

Genes:

CYLD-AS1:CYLD antisense RNA 1 [Gene - HGNC]
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.2974C>T (p.Arg992Ter)

HGVS:

NC_000016.10:g.50731751C>T
NG_007508.1:g.39613C>T
NM_001293557.2:c.2974C>T
NM_001370466.1:c.2974C>TMANE SELECT
NM_022162.3:c.3055C>T
NP_001280486.1:p.Arg992Ter
NP_001357395.1:p.Arg992Ter
NP_071445.1:p.Arg1019Ter
LRG_177t1:c.3055C>T
LRG_177:g.39613C>T
NC_000016.9:g.50765662C>T
NM_022162.1:c.3055C>T
NR_163434.1:n.3186C>T

Protein change:

R1019*

Links:

dbSNP: rs104895491

NCBI 1000 Genomes Browser:

rs104895491

Molecular consequence:

NR_163434.1:n.3186C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001293557.2:c.2974C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370466.1:c.2974C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_022162.3:c.3055C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Blau syndrome (BLAUS)
Synonyms:: Synovitis granulomatous with uveitis and cranial neuropathies; Arthrocutaneouveal granulomatosis; Granulomatosis, familial, Blau type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008523; MedGen: C5201146; Orphanet: 90340; OMIM: 186580

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000116262	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	no classification provided	not provided	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV004047954	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV000116262

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

no classification provided

not provided

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

SCV004047954

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

clinical testing

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

Description

also involved in OMIM 186580 and 266600: SCV000116262

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	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Novel CARD15/NOD2 mutations in Finnish patients with Crohn's disease and their relation to phenotypic variation in vitro and in vivo.

Lappalainen M, Paavola-Sakki P, Halme L, Turunen U, Färkkilä M, Repo H, Kontula K.

Inflamm Bowel Dis. 2008 Feb;14(2):176-85.

PubMed [citation]

PMID:: 17941079

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 Unité médicale des maladies autoinflammatoires, CHRU Montpellier, SCV000116262.1

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

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047954.1

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

Description

The stop gained variant c.2974C>T (p.Arg992Ter) in NOD2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2974C>T variant is reported with allele frequency of 0.002% in gnomAD exomes and novel in 1000 Genomes. The nucleotide change c.2974C>T in NOD2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Uncertain Significance

#	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 6, 2024

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