The NOD2 NM_001370466.1:c.2938dup (NP_001357395.1:p.(Leu980ProfsTer2)) frameshift variant has not previously been reported in somatic cancers (COSMIC). This variant is predicted to result in an absent or disrupted protein product. Based on available guidelines, this variant is considered to be Pathogenic.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.NOD2 encodes an immune-system protein that recognizes components of bacterial cell walls and helps activate inflammatory signaling. Changes in NOD2 are associated with Crohn disease and Blau syndrome. NOD2 is not known to have a specific established role in cancer.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met at strong: the p.(L980Pfs*2) frameshift has a stop 32 nucleotides before the exon-11/exon-12 junction, triggering the NMD-escape downgrade.
Met: homozygous genotype relative risk 42.1 with 95% CI 4.3–infinity exceeds the PS4 >5 threshold and excludes 1 in Crohn disease cases versus controls.
No benign criterion marked as applied in the recorded assessment.
Pathogenic: PVS1 strong plus PS4 strong satisfy the generic ACMG/AMP rule requiring two strong pathogenic criteria.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 29,257 / 1,613,186 alleles. Recorded AF 0.0181362. Recorded homozygote count 607.
This variant is present in gnomAD v2.1 (AF= 0.0152001; MAF= 1.52001%, 4298/282762 alleles, homozygotes = 115) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0342532; MAF= 3.42532%, 355/10364 alleles, homozygotes = 16); grpmax FAF= 0.0239652.
This variant is present in gnomAD-Canada v1.0 (AF= 0.01857282502443793, 342/18414 alleles, homozygotes = 3).
Recorded SpliceAI maximum delta score: 0.055. Refer to the recorded PP3/BP4 rationale for interpretation.
6 Uncertain significance · 3 Likely benign · 2 Likely Pathogenic · 1 Benign · 1 association · 1 Pathogenic · 1 Likely risk allele · 1 Established risk allele. ClinVar API review status: criteria provided, conflicting classifications.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 4 not met · 12 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
PS2, PM6, PP1, and BS4 are not assessed because the case lacks a documented proband-parent trio, affected-relative genotypes and phenotypes, informative meioses, or exact-variant family segregation results.
Reviewed NOD2 family studies concern different variants and cannot be transferred to NM_001370466.1:c.2938dup.
Neither PS3 nor BS3 is assessed because the available functional literature concerns different NOD2 variants and does not provide direct validated functional evidence for c.2938dup/p.(Leu980ProfsTer2).
PS4 is met from a verified case-control study of the same genomic NOD2 insertion allele: homozygous Crohn disease cases had reported genotype relative risk 42.1 (95% CI 4.3–infinity), satisfying RR >5 with a confidence interval excluding 1.
PP4 and BP5 were not assessed because the available record lacks the patient-level phenotype/family-history specificity and alternate-molecular-basis documentation required by their definitions.
PP5 and BP6 were not met because ClinVar variation 4691 has no expert-panel submission; ordinary laboratory assertions and aggregate classifications are excluded.
Neither PM3 nor BP2 can be assessed because the supplied evidence lacks a pathogenic partner allele and family-level phase information.
Population evidence does not support BA1 or PM2: the variant is common in the specified gnomAD control datasets, but its required grpmax FAF remains below 0.05.
BS1 requires disorder-specific maximum-credible-frequency assessment because NOD2/Crohn disease is a susceptibility phenotype with ancestry-related frequency enrichment and incomplete penetrance; BS2 cannot be established from gnomAD homozygote counts without healthy-adult and penetrance data.
No criteria match.
NM_001370466.1:c.2938dup is a frameshift in the MANE Select NOD2 transcript, producing NP_001357395.1:p.(L980Pfs*2). NOD2 loss of function is supported as a germline disease mechanism in the case evidence. The variant is in exon 11, and the predicted premature termination occurs 32 nucleotides before the exon-11/exon-12 junction, placing it in the generic ClinGen SVI NMD-escape region and triggering a one-tier downgrade from very strong to strong. The truncation affects the C-terminal leucine-rich-repeat region rather than an established non-critical terminal segment, so no additional non-critical-exon or distal-region downgrade is applied. Direct RNA evidence of transcript decay or escape was not available, so the inferred NMD behavior warrants human review.
PVS1: Null variant (nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function (LOF) is a known mechanism of disease.
The Hampe et al. case-control study evaluated the same recurrent NOD2 exon-11 C-insertion allele represented for this case as NC_000016.9:g.50763781dup / chr16:50729867 G>GC (rs2066847; alternate transcript nomenclature NM_022162.3:c.3019dup, p.Leu1007fs). Among sporadic Crohn disease cases, 20/304 were homozygous compared with 0/272 controls; the study reports genotype relative risk 42.1 with 95% CI 4.3–infinity, which excludes 1. For all carriers, the extracted counts were 77/304 cases versus 24/272 controls; I computed the carrier OR as 3.51 (95% CI 2.14–5.73), below the >5 threshold, but the prespecified PS4 rule permits RR or OR and the homozygous genotype relative risk meets the required >5 and CI-not-including-1 condition. The literature_pass packet had no ai_classified_papers, so there were no classifier PS4 leads requiring separate verification; the full text of PMID:11425413 was directly verified.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
PM2 is not met. The generic supporting threshold supplied for this case is <=0.0001, whereas the specified population sources show the variant at AF 0.0146597 in gnomAD v2.1 non-cancer exomes, AF 0.014827 in gnomAD v3.1 non-cancer genomes, and AF 0.0181362 in gnomAD v4.1 all-comers. These frequencies are far above the PM2 threshold and the variant is not absent from controls.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
PP5 is not met because ClinVar variation 4691 has no expert-panel submissions; the record contains conflicting ordinary laboratory submissions and aggregate classifications, which are explicitly excluded from triggering PP5.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
BA1 is not met. The governing default threshold is >=0.05, and the required filtering frequency is the grpmax FAF rather than a popmax point estimate. In the specified non-cancer exome-only gnomAD v2.1 data, grpmax FAF is 0.0239652; in gnomAD v4.1 all-comers, grpmax FAF is 0.02141027; and in gnomAD v3.1 non-cancer genomes, grpmax FAF is 0.02212918. All are below 0.05. The high Ashkenazi Jewish popmax point estimates do not replace the required grpmax FAF metric.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BP6 is not met because ClinVar variation 4691 has no expert-panel submissions; ordinary laboratory benign submissions and aggregate ClinVar labels are not sufficient under the stated BP6 rule.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
No proband-level de novo observation is documented, and there is no evidence that both maternity and paternity were confirmed. The available literature concerns other NOD2 variants and does not establish de novo occurrence of NM_001370466.1:c.2938dup.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
No well-established functional assay of NOD2 c.2938dup (p.(Leu980ProfsTer2)) was identified. The available functional studies evaluated other NOD2 variants, especially the distinct L1007fs/3020insC frameshift, and their results cannot be transferred to this variant without direct assay evidence; therefore PS3 is not assessed.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
The available case evidence does not provide parent or offspring testing, affected-proband observations, or any other phasing result showing NM_001370466.1:c.2938dup in trans with a pathogenic variant. The inheritance context for applying a recessive PM3 assessment is also not established in the supplied evidence.
For recessive disorders, detected in trans with a pathogenic variant ... This requires testing of parents (or offspring) to determine phase.
No assumed de novo occurrence is documented for NM_001370466.1:c.2938dup. The available evidence does not identify an affected proband with an apparently absent parental variant or provide parental testing information.
Assumed de novo, but without confirmation of paternity and maternity.
No affected family members carrying NM_001370466.1:c.2938dup and no meioses or segregation analysis for this exact variant are documented. The reviewed NOD2 literature concerns other variants, including 3020insC/1007fs, and therefore cannot establish co-segregation for c.2938dup; one reviewed study describes Crohn disease as a multifactorial trait.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. ... May be used as stronger evidence with increasing segregation data.
The available case evidence does not provide the patient's phenotype or family history in sufficient detail to determine whether it is highly specific for a single-gene disease. NOD2-associated Crohn disease susceptibility is not, by itself, a highly specific phenotype with a single genetic etiology.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
BS1 is not assessed from the generic 1% default alone. The required filtering frequencies exceed 1% (grpmax FAF 0.0239652 in non-cancer gnomAD v2.1 exomes, 0.02212918 in non-cancer gnomAD v3.1 genomes, and 0.02141027 in gnomAD v4.1 all-comers), but NOD2-associated Crohn disease is a susceptibility phenotype with ancestry-related enrichment and incomplete penetrance rather than an established fully penetrant early-onset Mendelian disorder. No case-specific maximum-credible-frequency calculation with quantified prevalence, penetrance, allelic heterogeneity, and inheritance inputs is available, so BS1 cannot be applied solely because the frequency exceeds 1%.
Allele frequency is greater than expected for the disorder.
BS2 is not assessed. The population datasets report homozygotes (103 in gnomAD v2.1 non-cancer exomes, 28 in gnomAD v3.1 non-cancer genomes, and 607 in gnomAD v4.1 all-comers), but those records do not establish that the individuals were healthy adults, clinically unaffected for Crohn disease, or observed in a disorder expected to be fully penetrant at an early age. Population homozygote counts alone therefore do not satisfy the BS2 definition.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
No well-established functional assay of NOD2 c.2938dup (p.(Leu980ProfsTer2)) demonstrating no damaging effect on protein function or splicing was identified. The available studies evaluated other NOD2 variants, especially the distinct L1007fs/3020insC frameshift, so they cannot establish BS3 for this variant; therefore BS3 is not assessed.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
No affected family members have been documented for this case, and there are no genotype results showing that NM_001370466.1:c.2938dup fails to segregate with disease. Therefore lack of segregation cannot be evaluated, including the possibility of phenocopies or more than one pathogenic variant in a family.
Lack of segregation in affected members of a family.
The available case evidence does not document NM_001370466.1:c.2938dup in trans with a pathogenic variant in a fully penetrant dominant disorder, or in cis with a pathogenic variant in any inheritance pattern. No family-level phase data are supplied.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
No case-level evidence in the available materials establishes that this variant was found in a patient with an alternate molecular basis for disease. Population frequency and conflicting ClinVar submissions do not satisfy BP5.
Variant found in a case with an alternate molecular basis for disease.
PS1 (Richards et al. 2015, PMID:25741868) requires the same amino acid change as a previously established pathogenic variant, evaluated regardless of the underlying nucleotide change. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, no altered amino acid exists at this position to compare against any previously established pathogenic missense variant, so PS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PS1 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PM1 (Richards et al. 2015, PMID:25741868) applies to a missense variant located in a mutational hot spot and/or a critical, well-established functional domain without benign variation. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, no altered residue exists to evaluate for mutational hot-spot or critical-domain membership, so PM1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM1 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
PM5 (Richards et al. 2015, PMID:25741868) requires a novel missense change at an amino acid residue where a different missense change has previously been determined to be pathogenic. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, no missense change exists at this residue to compare against a different pathogenic missense change at the same position, so PM5's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM5 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PP2 (Richards et al. 2015, PMID:25741868) applies to a missense variant in a gene with a low rate of benign missense variation, where missense variants are a common mechanism of disease. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, the gene's missense-constraint properties are irrelevant because no missense change is present to evaluate, so PP2's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PP2 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PP3 is not applicable because NM_001370466.1:c.2938dup is a frameshift variant, predicted as NP_001357395.1:p.(L980Pfs*2). Under the governing scope, PP3 applies only to missense or intronic/splice-region variants, not frameshift or other protein-length-changing variants. The available SpliceAI max delta of 0.055 is therefore not used to assign PP3, and no REVEL score is applicable.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP1 (Richards et al. 2015, PMID:25741868) applies to a missense variant in a gene for which primarily truncating variants are known to cause disease. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, the gene's truncating-variant mechanism is irrelevant because no missense change is present to evaluate, so BP1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP1 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP4 is not applicable because NM_001370466.1:c.2938dup is a frameshift variant, predicted as NP_001357395.1:p.(L980Pfs*2). Under the governing scope, BP4 applies only to missense or intronic/splice-region variants, not frameshift or other protein-length-changing variants; a no-impact splice prediction cannot negate the truncating protein effect. The available SpliceAI max delta of 0.055 is therefore not used to assign BP4.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc) ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in NOD2, mapped onto the exon structure of NM_001370466.1. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Ashkenazi Jewish940 / 29,570 | 0.03234 hom |
| Amish28 / 912 | 0.031 |
| European (non-Finnish)25512 / 1,179,300 | 0.022527 hom |
| European (Finnish)977 / 63,982 | 0.01512 hom |
| Remaining individuals861 / 62,438 | 0.01425 hom |
| Admixed American560 / 60,002 | 0.00936 hom |
| African/African American222 / 75,020 | 0.0032 hom |
| Middle Eastern16 / 6,052 | 0.0026 |
| South Asian138 / 91,054 | 0.00151 hom |
| East Asian3 / 44,856 | 6.7e-05 |
| Ashkenazi Jewish355 / 10,364 | 0.03416 hom |
| European (non-Finnish)3012 / 129,102 | 0.02392 hom |
| European (Finnish)398 / 25,124 | 0.0165 hom |
| Remaining individuals114 / 7,224 | 0.016 |
| Admixed American301 / 35,420 | 0.00852 hom |
| African/African American71 / 24,966 | 0.0028 |
| South Asian47 / 30,614 | 0.0015 |
This variant is present in gnomAD v4.1 (AF= 0.0181362; MAF= 1.81362%, 29257/1613186 alleles, homozygotes = 607) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.031789; MAF= 3.17890%, 940/29570 alleles, homozygotes = 34); grpmax FAF= 0.0214103.
This variant is present in gnomAD v2.1 (AF= 0.0152001; MAF= 1.52001%, 4298/282762 alleles, homozygotes = 115) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0342532; MAF= 3.42532%, 355/10364 alleles, homozygotes = 16); grpmax FAF= 0.0239652.
This variant is present in gnomAD-Canada v1.0 (AF= 0.01857282502443793, 342/18414 alleles, homozygotes = 3).
PP3 is not applicable because NM_001370466.1:c.2938dup is a frameshift variant, predicted as NP_001357395.1:p.(L980Pfs*2). Under the governing scope, PP3 applies only to missense or intronic/splice-region variants, not frameshift or other protein-length-changing variants. The available SpliceAI max delta of 0.055 is therefore not used to assign PP3, and no REVEL score is applicable.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP4 is not applicable because NM_001370466.1:c.2938dup is a frameshift variant, predicted as NP_001357395.1:p.(L980Pfs*2). Under the governing scope, BP4 applies only to missense or intronic/splice-region variants, not frameshift or other protein-length-changing variants; a no-impact splice prediction cannot negate the truncating protein effect. The available SpliceAI max delta of 0.055 is therefore not used to assign BP4.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc) ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_001370466.1:c.2938dup in NOD2 is a frameshift variant predicted to produce NP_001357395.1:p.(Leu980ProfsTer2). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for NOD2, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).
8 paper records listed. 2 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.
A C-insertion mutation identified in exon 11 in the region coding for the leucine-rich region leads to a premature stop codon at aminoacid 1007 of the encoded protein.
Location Methods, paragraph describing mutation selection; Table 3; Discussion
Context NOD2 coding-region mutation screening and genotyping in affected individuals, families, trios, and normal controls; association analyses for Crohn disease and ulcerative colitis.
Certain types of variants (e.g. nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single exon or multi-exon deletion) can often be assumed to disrupt gene function by leading to complete absence of the gene product by lack of transcription or nonsense-mediated decay of an altered transcript.
Location Proposed Criteria for Interpretation of Sequence Variants, PVS1 Null variants
Context ACMG/AMP sequence-variant interpretation guideline; general framework rather than a variant-specific experiment.
Following a frameshift mutation (caused by a cytosine insertion and known as 3020insC or single-nucleotide polymorphism (SNP)13) leading to the truncation of the leucine-rich repeat region of NOD2, responsiveness to bacterial lipopolysaccharide (LPS) was observed to be greatly diminished.
Introduction; Results, ‘NOD2 SNP analysis’ and ‘NOD2 SNPs and predominant disease distribution’
The LRR domain of the gene has a binding activity for bacterial peptidoglycans, and mutations in this domain abrogate nuclear factor-kB–mediated signaling (Inohara et al. 1999, 2000; Chamaillard et al. 2002).
Introduction, page 624
However the NOD2-R702W and NOD2-L1007fs variant proteins seemingly lose their ability to interact with vimentin (Figure 2C).
Results, ‘The LRR domain of NOD2 is the major determinant for binding with vimentin and common CD-associated polymorphisms disrupt this interaction’
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.0181362; MAF= 1.81362%, 29257/1613186 alleles, homozygotes = 607) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.031789; MAF= 3.17890%, 940/29570 alleles, homozygotes = 34); grpmax FAF= 0.0214103.
This variant is present in gnomAD v2.1 (AF= 0.0152001; MAF= 1.52001%, 4298/282762 alleles, homozygotes = 115) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0342532; MAF= 3.42532%, 355/10364 alleles, homozygotes = 16); grpmax FAF= 0.0239652.
This variant is present in gnomAD-Canada v1.0 (AF= 0.01857282502443793, 342/18414 alleles, homozygotes = 3).
This variant has been reported in ClinVar as Uncertain significance (6 clinical laboratories) and as Likely benign (3 clinical laboratories) and as Likely Pathogenic (2 clinical laboratories) and as Benign (1 clinical laboratory) and as association (1 clinical laboratory) and as Pathogenic (1 clinical laboratory) and as Likely risk allele (1 clinical laboratory) and as Established risk allele (1 clinical laboratory). (ClinVarID = 4691)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.