16-50712018-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001370466.1(NOD2):c.2026C>T(p.Arg676Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00395 in 1,613,156 control chromosomes in the GnomAD database, including 20 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
Consequence
NM_001370466.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOD2 | NM_001370466.1 | c.2026C>T | p.Arg676Cys | missense_variant | Exon 4 of 12 | ENST00000647318.2 | NP_001357395.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOD2 | ENST00000647318.2 | c.2026C>T | p.Arg676Cys | missense_variant | Exon 4 of 12 | NM_001370466.1 | ENSP00000495993.1 | |||
NOD2 | ENST00000300589.6 | c.2107C>T | p.Arg703Cys | missense_variant | Exon 4 of 12 | 1 | ENSP00000300589.2 | |||
NOD2 | ENST00000641284.2 | n.2026C>T | non_coding_transcript_exon_variant | Exon 4 of 6 | ENSP00000493088.1 | |||||
NOD2 | ENST00000646677.2 | n.2026C>T | non_coding_transcript_exon_variant | Exon 4 of 13 | ENSP00000496533.1 |
Frequencies
GnomAD3 genomes AF: 0.00330 AC: 503AN: 152266Hom.: 4 Cov.: 33
GnomAD3 exomes AF: 0.00321 AC: 798AN: 248652Hom.: 0 AF XY: 0.00317 AC XY: 428AN XY: 134888
GnomAD4 exome AF: 0.00402 AC: 5866AN: 1460772Hom.: 16 Cov.: 33 AF XY: 0.00393 AC XY: 2856AN XY: 726738
GnomAD4 genome AF: 0.00331 AC: 504AN: 152384Hom.: 4 Cov.: 33 AF XY: 0.00299 AC XY: 223AN XY: 74522
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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Observed in individuals with inflammatory bowel disease and other auto-inflammatory disorders (Lesage et al., 2002; Yao et al., 2012; Shen et al., 2015; Androletti et al., 2017; Burillo-Sanz et al., 2017; Li et al., 2020); Case control studies suggest this variant may be associated with Crohn's disease (Rivas et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in 0.32% (887/280050 alleles) in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32707200, 22942351, 26164256, 28814775, 28422189, 26070941, 11875755, 21983784, 33394828, 33927005, 35211104, 34975878) -
NOD2: BP4, BS1, BS2 -
not specified Benign:2
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Autoinflammatory syndrome Uncertain:1
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Regional enteritis;C5201146:Blau syndrome Benign:1
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Inflammatory bowel disease 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Blau syndrome Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at