8-102212829-G-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_015713.5(RRM2B):c.850C>T(p.Gln284Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,832 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
RRM2B
NM_015713.5 stop_gained
NM_015713.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 8.00
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]
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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 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.195 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 8-102212829-G-A is Pathogenic according to our data. Variant chr8-102212829-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 5386.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RRM2B | NM_015713.5 | c.850C>T | p.Gln284Ter | stop_gained | 8/9 | ENST00000251810.8 | NP_056528.2 | |
RRM2B | NM_001172477.1 | c.1066C>T | p.Gln356Ter | stop_gained | 8/9 | NP_001165948.1 | ||
RRM2B | NM_001172478.2 | c.694C>T | p.Gln232Ter | stop_gained | 7/8 | NP_001165949.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RRM2B | ENST00000251810.8 | c.850C>T | p.Gln284Ter | stop_gained | 8/9 | 1 | NM_015713.5 | ENSP00000251810 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250450Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135420
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459832Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 726352
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mitochondrial DNA depletion syndrome 8a Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2007 | - - |
RRM2B-related mitochondrial disease Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A;A
Vest4
ClinPred
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at