chr2-108729132-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS2_Supporting
The NM_006267.5(RANBP2):c.73A>G(p.Lys25Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,569,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006267.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.73A>G | p.Lys25Glu | missense_variant, splice_region_variant | 2/29 | ENST00000283195.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.73A>G | p.Lys25Glu | missense_variant, splice_region_variant | 2/29 | 1 | NM_006267.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000436 AC: 10AN: 229504Hom.: 0 AF XY: 0.0000240 AC XY: 3AN XY: 125248
GnomAD4 exome AF: 0.0000106 AC: 15AN: 1417598Hom.: 0 Cov.: 31 AF XY: 0.00000709 AC XY: 5AN XY: 705180
GnomAD4 genome AF: 0.000105 AC: 16AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74494
ClinVar
Submissions by phenotype
Familial acute necrotizing encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 17, 2023 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 25 of the RANBP2 protein (p.Lys25Glu). This variant is present in population databases (rs576251747, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 650442). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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