2-108753951-A-G
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_006267.5(RANBP2):āc.2182A>Gā(p.Asn728Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,611,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_006267.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.2182A>G | p.Asn728Asp | missense_variant | 15/29 | ENST00000283195.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.2182A>G | p.Asn728Asp | missense_variant | 15/29 | 1 | NM_006267.5 | P1 | |
RANBP2 | ENST00000697737.1 | c.2182A>G | p.Asn728Asp | missense_variant | 15/27 | ||||
RANBP2 | ENST00000697740.1 | c.2104A>G | p.Asn702Asp | missense_variant | 15/27 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249494Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135420
GnomAD4 exome AF: 0.0000295 AC: 43AN: 1459634Hom.: 0 Cov.: 34 AF XY: 0.0000275 AC XY: 20AN XY: 726122
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74382
ClinVar
Submissions by phenotype
Familial acute necrotizing encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2017 | This sequence change replaces asparagine with aspartic acid at codon 728 of the RANBP2 protein (p.Asn728Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a RANBP2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on RANBP2 function. The available evidence is currently insufficient to determine its role 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