rs121918308
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The ENST00000251810.8(RRM2B):āc.580G>Cā(p.Glu194Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,452 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E194G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000251810.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RRM2B | NM_015713.5 | c.580G>C | p.Glu194Gln | missense_variant | 6/9 | ENST00000251810.8 | NP_056528.2 | |
RRM2B | NM_001172477.1 | c.796G>C | p.Glu266Gln | missense_variant | 6/9 | NP_001165948.1 | ||
RRM2B | NM_001172478.2 | c.424G>C | p.Glu142Gln | missense_variant | 5/8 | NP_001165949.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RRM2B | ENST00000251810.8 | c.580G>C | p.Glu194Gln | missense_variant | 6/9 | 1 | NM_015713.5 | ENSP00000251810 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251316Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135822
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461452Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727062
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 16, 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RRM2B protein function. This variant has not been reported in the literature in individuals affected with RRM2B-related conditions. This variant is present in population databases (rs121918308, gnomAD 0.006%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 194 of the RRM2B protein (p.Glu194Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at