rs515726199
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_015713.5(RRM2B):c.950delT(p.Leu317fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
RRM2B
NM_015713.5 frameshift
NM_015713.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
RRM2B (HGNC:17296): (ribonucleotide reductase regulatory TP53 inducible subunit M2B) This gene encodes the small subunit of a p53-inducible ribonucleotide reductase. This heterotetrameric enzyme catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. The product of this reaction is necessary for DNA synthesis. Mutations in this gene have been associated with autosomal recessive mitochondrial DNA depletion syndrome, autosomal dominant progressive external ophthalmoplegia-5, and mitochondrial neurogastrointestinal encephalopathy. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.1 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-102208238-TA-T is Pathogenic according to our data. Variant chr8-102208238-TA-T is described in ClinVar as [Pathogenic]. Clinvar id is 30432.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RRM2B | NM_015713.5 | c.950delT | p.Leu317fs | frameshift_variant | Exon 9 of 9 | ENST00000251810.8 | NP_056528.2 | |
| RRM2B | NM_001172477.1 | c.1166delT | p.Leu389fs | frameshift_variant | Exon 9 of 9 | NP_001165948.1 | ||
| RRM2B | NM_001172478.2 | c.794delT | p.Leu265fs | frameshift_variant | Exon 8 of 8 | NP_001165949.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1442234Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1AN XY: 718774
GnomAD4 exome
AF:
AC:
1
AN:
1442234
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
718774
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mitochondrial disease Pathogenic:1
Apr 07, 2017
Wellcome Centre for Mitochondrial Research, Newcastle University
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 Pathogenic:1
Jun 07, 2011
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
RRM2B-related mitochondrial disease Other:1
-
GeneReviews
Significance: not provided
Review Status: no classification provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at