1-26912001-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2
The NM_021969.3(NR0B2):c.618G>A(p.Trp206*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,072 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 (no stars).
Frequency
Consequence
NM_021969.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NR0B2 | ENST00000254227.4 | c.618G>A | p.Trp206* | stop_gained | Exon 2 of 2 | 1 | NM_021969.3 | ENSP00000254227.3 | ||
NUDC | ENST00000435827.6 | c.93+766C>T | intron_variant | Intron 3 of 6 | 5 | ENSP00000404020.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251398Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135880
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727242
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
NR0B2-related disorder Uncertain:1
The NR0B2 c.618G>A variant is predicted to result in premature protein termination (p.Trp206*). This variant was reported in two patients with type 2 diabetes and BMI of 24.1 +/- 4.0 kg/m2 and was also identified in one individual from a control population (Enya et al. 2008. PubMed ID: 18781616). Additional functional studies showed that the p.Trp206* variant altered protein function (Enya et al. 2008. PubMed ID: 18781616). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-27238492-C-T). This variant is located in the terminal exon of NROB2. Early termination changes upstream but not downstream of this change have been reported as causative. While we suspect this variant may be causative, at this time, its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at