rs761286207
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005619.5(RTN2):c.745G>C(p.Glu249Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,612,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. E249K) has been classified as Uncertain significance.
Frequency
Consequence
NM_005619.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTN2 | NM_005619.5 | c.745G>C | p.Glu249Gln | missense_variant | 4/11 | ENST00000245923.9 | |
RTN2 | NM_206900.3 | c.745G>C | p.Glu249Gln | missense_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTN2 | ENST00000245923.9 | c.745G>C | p.Glu249Gln | missense_variant | 4/11 | 1 | NM_005619.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249532Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134902
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1460148Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 726392
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 528003). This variant has not been reported in the literature in individuals affected with RTN2-related conditions. This variant is present in population databases (rs761286207, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 249 of the RTN2 protein (p.Glu249Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at