rs104895426
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_001370466.1(NOD2):c.821C>T(p.Ala274Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000533 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A274A) has been classified as Likely benign.
Frequency
Consequence
NM_001370466.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOD2 | NM_001370466.1 | c.821C>T | p.Ala274Val | missense_variant | 4/12 | ENST00000647318.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOD2 | ENST00000647318.2 | c.821C>T | p.Ala274Val | missense_variant | 4/12 | NM_001370466.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 250916Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135746
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461802Hom.: 0 Cov.: 39 AF XY: 0.0000426 AC XY: 31AN XY: 727194
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74322
ClinVar
Submissions by phenotype
Regional enteritis;C5201146:Blau syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 301 of the NOD2 protein (p.Ala301Val). This variant is present in population databases (rs104895426, gnomAD 0.01%). This missense change has been observed in individual(s) with Crohn disease (PMID: 11385576). ClinVar contains an entry for this variant (Variation ID: 97884). 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 with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Blau syndrome Other:1
not provided, no classification provided | literature only | Unité médicale des maladies autoinflammatoires, CHRU Montpellier | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at