16-50722863-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001370466.1(NOD2):c.2717+158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,166 control chromosomes in the GnomAD database, including 1,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.11 ( 1256 hom., cov: 32)
Consequence
NOD2
NM_001370466.1 intron
NM_001370466.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.58
Genes affected
NOD2 (HGNC:5331): (nucleotide binding oligomerization domain containing 2) This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOD2 | NM_001370466.1 | c.2717+158C>T | intron_variant | ENST00000647318.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOD2 | ENST00000647318.2 | c.2717+158C>T | intron_variant | NM_001370466.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.109 AC: 16605AN: 152048Hom.: 1256 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.109 AC: 16599AN: 152166Hom.: 1256 Cov.: 32 AF XY: 0.103 AC XY: 7677AN XY: 74390
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1Benign:5Other:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Yao syndrome Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Aug 18, 2020 | - - |
risk factor, no assertion criteria provided | literature only | OMIM | Apr 01, 2004 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 24, 2019 | This variant is associated with the following publications: (PMID: 26164256, 29248579, 28750667, 19426395, 21914217, 23584365, 23102769, 12577202, 24682985) - |
Autoinflammatory syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Breda Genetics srl | Nov 05, 2019 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
Blau syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2004 | - - |
Blau syndrome;CN260071:Inflammatory bowel disease 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2020 | - - |
Inflammatory bowel disease 1 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Apr 01, 2004 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at