rs387906891
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015713.5(RRM2B):c.817G>A(p.Gly273Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,607,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015713.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRM2B | NM_015713.5 | c.817G>A | p.Gly273Ser | missense_variant | 8/9 | ENST00000251810.8 | |
RRM2B | NM_001172477.1 | c.1033G>A | p.Gly345Ser | missense_variant | 8/9 | ||
RRM2B | NM_001172478.2 | c.661G>A | p.Gly221Ser | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRM2B | ENST00000251810.8 | c.817G>A | p.Gly273Ser | missense_variant | 8/9 | 1 | NM_015713.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249846Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135172
GnomAD4 exome AF: 0.0000419 AC: 61AN: 1455000Hom.: 0 Cov.: 27 AF XY: 0.0000345 AC XY: 25AN XY: 724380
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74272
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function This variant is associated with the following publications: (PMID: 23107649, 21646632) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 28, 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 30435). This missense change has been observed in individuals with RRM2B-related conditions (PMID: 23107649, 32161153). This variant is present in population databases (rs387906891, gnomAD 0.005%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 273 of the RRM2B protein (p.Gly273Ser). - |
Progressive external ophthalmoplegia Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jun 07, 2011 | - - |
RRM2B-related mitochondrial disease Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at