chr11-14281689-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_012250.6(RRAS2):c.440G>A(p.Arg147Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,596,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R147W) has been classified as Uncertain significance.
Frequency
Consequence
NM_012250.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRAS2 | NM_012250.6 | c.440G>A | p.Arg147Gln | missense_variant | 5/6 | ENST00000256196.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRAS2 | ENST00000256196.9 | c.440G>A | p.Arg147Gln | missense_variant | 5/6 | 1 | NM_012250.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000385 AC: 9AN: 233568Hom.: 0 AF XY: 0.0000237 AC XY: 3AN XY: 126530
GnomAD4 exome AF: 0.0000138 AC: 20AN: 1444212Hom.: 0 Cov.: 30 AF XY: 0.00000975 AC XY: 7AN XY: 717934
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 01, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 147 of the RRAS2 protein (p.Arg147Gln). 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. 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. This variant has not been reported in the literature in individuals affected with RRAS2-related conditions. This variant is present in population databases (rs377321245, gnomAD 0.02%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at