16-50711313-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_001370466.1(NOD2):c.1321C>T(p.Arg441Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R441H) has been classified as Likely benign.
Frequency
Consequence
NM_001370466.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOD2 | NM_001370466.1 | c.1321C>T | p.Arg441Cys | missense_variant | 4/12 | ENST00000647318.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOD2 | ENST00000647318.2 | c.1321C>T | p.Arg441Cys | missense_variant | 4/12 | NM_001370466.1 | P1 | ||
NOD2 | ENST00000300589.6 | c.1402C>T | p.Arg468Cys | missense_variant | 4/12 | 1 | |||
NOD2 | ENST00000641284.2 | c.1321C>T | p.Arg441Cys | missense_variant, NMD_transcript_variant | 4/6 | ||||
NOD2 | ENST00000646677.2 | c.1321C>T | p.Arg441Cys | missense_variant, NMD_transcript_variant | 4/13 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250136Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135460
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461310Hom.: 0 Cov.: 34 AF XY: 0.0000399 AC XY: 29AN XY: 726988
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 03, 2019 | - - |
Regional enteritis;C5201146:Blau syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 468 of the NOD2 protein (p.Arg468Cys). 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. 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 not expected to disrupt NOD2 protein function. ClinVar contains an entry for this variant (Variation ID: 1163981). This variant has not been reported in the literature in individuals affected with NOD2-related conditions. This variant is present in population databases (rs769988393, gnomAD 0.02%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at