NM_001370466.1(NOD2):c.1929C>A (p.Asn643Lys) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 17, 2023
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:: RCV002513874.10

Allele description [Variation Report for NM_001370466.1(NOD2):c.1929C>A (p.Asn643Lys)]

NM_001370466.1(NOD2):c.1929C>A (p.Asn643Lys)

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.1929C>A (p.Asn643Lys)

HGVS:

NC_000016.10:g.50711921C>A
NG_007508.1:g.19783C>A
NM_001293557.2:c.1929C>A
NM_001370466.1:c.1929C>AMANE SELECT
NM_022162.3:c.2010C>A
NP_001280486.1:p.Asn643Lys
NP_001357395.1:p.Asn643Lys
NP_071445.1:p.Asn670Lys
LRG_177t1:c.2010C>A
LRG_177:g.19783C>A
NC_000016.9:g.50745832C>A
NM_022162.1:c.2010C>A
NR_163434.1:n.1994C>A
Q9HC29:p.Asn670Lys

Protein change:

N643K

Links:

UniProtKB: Q9HC29#VAR_073242; dbSNP: rs104895475

NCBI 1000 Genomes Browser:

rs104895475

Molecular consequence:

NM_001293557.2:c.1929C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.1929C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.2010C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.1994C>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:: Regional enteritis
Synonyms:: Enteritis, Granulomatous
Identifiers:: MeSH: D003424; MedGen: C0678202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001576119	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 32647028, 15459013, 20039400, 25093298, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576119

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (5)
[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

Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation.

Matsuda T, Kambe N, Ueki Y, Kanazawa N, Izawa K, Honda Y, Kawakami A, Takei S, Tonomura K, Inoue M, Kobayashi H, Okafuji I, Sakurai Y, Kato N, Maruyama Y, Inoue Y, Otsubo Y, Makino T, Okada S, Kobayashi I, Yashiro M, Ito S, et al.

Ann Rheum Dis. 2020 Nov;79(11):1492-1499. doi: 10.1136/annrheumdis-2020-217320. Epub 2020 Jul 9.

PubMed [citation]

PMID:: 32647028

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome.

Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S, Fuji A, Yuasa T, Manki A, Sakurai Y, Nakajima M, Kobayashi H, Fujiwara I, Tsutsumi H, Utani A, Nishigori C, Heike T, Nakahata T, Miyachi Y.

Blood. 2005 Feb 1;105(3):1195-7. Epub 2004 Sep 30.

PubMed [citation]

PMID:: 15459013

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576119.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 670 of the NOD2 protein (p.Asn670Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Blau syndrome or early onset sarcoidosis (PMID: 15459013, 20039400, 32647028). ClinVar contains an entry for this variant (Variation ID: 97842). 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 NOD2 protein function. Experimental studies have shown that this missense change affects NOD2 function (PMID: 15459013, 20039400, 25093298). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 13, 2024

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