NM_001370466.1(NOD2):c.2852G>A (p.Gly951Glu) AND multiple conditions

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 3, 2021
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:: RCV001247472.4

Allele description

NM_001370466.1(NOD2):c.2852G>A (p.Gly951Glu)

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.2852G>A (p.Gly951Glu)

HGVS:

NC_000016.10:g.50725539G>A
NG_007508.1:g.33401G>A
NM_001293557.2:c.2852G>A
NM_001370466.1:c.2852G>AMANE SELECT
NM_022162.3:c.2933G>A
NP_001280486.1:p.Gly951Glu
NP_001357395.1:p.Gly951Glu
NP_071445.1:p.Gly978Glu
LRG_177t1:c.2933G>A
LRG_177:g.33401G>A
NC_000016.9:g.50759450G>A
NM_022162.1:c.2933G>A
NM_022162.2:c.2933G>A
NR_163434.1:n.3064G>A

Protein change:

G951E

Links:

dbSNP: rs104895457

NCBI 1000 Genomes Browser:

rs104895457

Molecular consequence:

NM_001293557.2:c.2852G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.2852G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.2933G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.3064G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Name:: Inflammatory bowel disease 1 (IBD1)
Synonyms:: Inflammatory bowel disease 1, Crohn disease; INFLAMMATORY BOWEL DISEASE (CROHN DISEASE) 1
Identifiers:: MONDO: MONDO:0009960; MedGen: CN260071; OMIM: 266600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001420897	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 3, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11875755, 15044951, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001420897

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 3, 2021)

germline

clinical testing

PubMed (3)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease.

Lesage S, Zouali H, Cézard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Binder V, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Merlin F, Chamaillard M, Jannot AS, Thomas G, Hugot JP; EPWG-IBD Group.; EPIMAD Group.; GETAID Group..

Am J Hum Genet. 2002 Apr;70(4):845-57. Epub 2002 Mar 1.

PubMed [citation]

PMID:: 11875755
PMCID:: PMC379113

Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition.

Tanabe T, Chamaillard M, Ogura Y, Zhu L, Qiu S, Masumoto J, Ghosh P, Moran A, Predergast MM, Tromp G, Williams CJ, Inohara N, Núñez G.

EMBO J. 2004 Apr 7;23(7):1587-97. Epub 2004 Mar 25.

PubMed [citation]

PMID:: 15044951
PMCID:: PMC391079

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001420897.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 978 of the NOD2 protein (p.Gly978Glu). This variant is present in population databases (rs104895457, gnomAD 0.01%). This missense change has been observed in individual(s) with Crohn's disease (PMID: 11875755). ClinVar contains an entry for this variant (Variation ID: 97872). 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 not expected to disrupt NOD2 protein function. Experimental studies have shown that this missense change does not substantially affect NOD2 function (PMID: 15044951). 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: Jan 21, 2023

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