rs545734771
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001370466.1(NOD2):c.2693A>G(p.Asp898Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001370466.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOD2 | NM_001370466.1 | c.2693A>G | p.Asp898Gly | missense_variant | 8/12 | ENST00000647318.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOD2 | ENST00000647318.2 | c.2693A>G | p.Asp898Gly | missense_variant | 8/12 | NM_001370466.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251474Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135908
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727248
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74504
ClinVar
Submissions by phenotype
NOD2-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 01, 2024 | The NOD2 c.2774A>G variant is predicted to result in the amino acid substitution p.Asp925Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | The c.2774A>G (p.D925G) alteration is located in exon 8 (coding exon 8) of the NOD2 gene. This alteration results from a A to G substitution at nucleotide position 2774, causing the aspartic acid (D) at amino acid position 925 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Regional enteritis;C5201146:Blau syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 925 of the NOD2 protein (p.Asp925Gly). This variant is present in population databases (rs545734771, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NOD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 581298). 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 with a negative predictive value of 95%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at