ClinVar Genomic variation as it relates to human health
NM_001370466.1(NOD2):c.1036C>T (p.Arg346Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(3); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370466.1(NOD2):c.1036C>T (p.Arg346Cys)
Variation ID: 97902 Accession: VCV000097902.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q12.1 16: 50711028 (GRCh38) [ NCBI UCSC ] 16: 50744939 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 20, 2014 Apr 15, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370466.1:c.1036C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357395.1:p.Arg346Cys missense NM_001293557.2:c.1036C>T NP_001280486.1:p.Arg346Cys missense NM_022162.3:c.1117C>T NP_071445.1:p.Arg373Cys missense NR_163434.1:n.1101C>T non-coding transcript variant NC_000016.10:g.50711028C>T NC_000016.9:g.50744939C>T NG_007508.1:g.18890C>T LRG_177:g.18890C>T LRG_177t1:c.1117C>T Q9HC29:p.Arg373Cys - Protein change
- R373C, R346C
- Other names
- -
- Canonical SPDI
- NC_000016.10:50711027:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Exome Aggregation Consortium (ExAC) 0.00017
The Genome Aggregation Database (gnomAD), exomes 0.00018
The Genome Aggregation Database (gnomAD) 0.00021
Trans-Omics for Precision Medicine (TOPMed) 0.00021
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NOD2 | - | - |
GRCh38 GRCh37 |
941 | 1037 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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not provided (1) |
no classification provided
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- | RCV000084160.8 | |
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
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Feb 1, 2024 | RCV001753488.19 | |
Likely benign (1) |
criteria provided, single submitter
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May 14, 2021 | RCV002262685.10 | |
Likely benign (1) |
criteria provided, single submitter
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Dec 12, 2023 | RCV002513891.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(May 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autoinflammatory syndrome
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002543016.1
First in ClinVar: Jul 09, 2022 Last updated: Jul 09, 2022 |
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Likely benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004139313.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
NOD2: BP4
Number of individuals with the variant: 2
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Uncertain significance
(Dec 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital
Accession: SCV002775021.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Nov 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001987702.2
First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023 |
Comment:
Identified in an individual with Crohn disease and an individual with spondylarthropathy, however, segregation information was not included (Lesage et al., 2002; Miceli-Richard et al., … (more)
Identified in an individual with Crohn disease and an individual with spondylarthropathy, however, segregation information was not included (Lesage et al., 2002; Miceli-Richard et al., 2002); Functional studies indicate that this variant does not affect NF-kB activation, however, further studies are warranted (Tanabe et al., 2004); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11385576, 31784737, 11875755, 15044951, 12115249) (less)
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Uncertain significance
(Jan 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004562960.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The NOD2 c.1117C>T; p.Arg373Cys variant (rs145293873), to our knowledge, is not reported in individuals with Blau syndrome, but is reported in the literature in individuals … (more)
The NOD2 c.1117C>T; p.Arg373Cys variant (rs145293873), to our knowledge, is not reported in individuals with Blau syndrome, but is reported in the literature in individuals affected with Crohn’s disease, spondyloarthropathy, or dermatitis (Lesage 2002, Miceli-Richard 2002, Taylan 2015). This variant is also reported in ClinVar (Variation ID: 97902) and is found in the general population with an overall allele frequency of 0.0184% (52/282,834 alleles) in the Genome Aggregation Database. In vitro functional analyses demonstrate wild-type function is retained (Tanabe 2004). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.231). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Lesage S et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002 Apr;70(4):845-57. PMID: 11875755. Miceli-Richard C et al. CARD15/NOD2 analyses in spondylarthropathy. Arthritis Rheum. 2002 May;46(5):1405-6. PMID: 12115249. Tanabe T et al. Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. EMBO J. 2004 Apr 7;23(7):1587-97. PMID: 15044951. Taylan F et al. Whole-exome sequencing of Ethiopian patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol. 2015 Aug;136(2):507-9.e19. PMID: 25819062. (less)
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Likely benign
(Dec 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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Regional enteritis
Blau syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000935827.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 28, 2024 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002034296.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002037688.1 First in ClinVar: Dec 21, 2021 Last updated: Dec 21, 2021 |
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not provided
(-)
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no classification provided
Method: not provided
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Sarcoidosis, early-onset
Affected status: not provided
Allele origin:
not provided
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Unité médicale des maladies autoinflammatoires, CHRU Montpellier
Accession: SCV000116291.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
also involved in OMIM 186580 and 266600
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs145293873 ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.