2-10124835-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001034.4(RRM2):c.554A>G(p.Lys185Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
RRM2
NM_001034.4 missense
NM_001034.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 9.22
Genes affected
RRM2 (HGNC:10452): (ribonucleotide reductase regulatory subunit M2) This gene encodes one of two non-identical subunits for ribonucleotide reductase. This reductase catalyzes the formation of deoxyribonucleotides from ribonucleotides. Synthesis of the encoded protein (M2) is regulated in a cell-cycle dependent fashion. Transcription from this gene can initiate from alternative promoters, which results in two isoforms that differ in the lengths of their N-termini. Related pseudogenes have been identified on chromosomes 1 and X. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39391354).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRM2 | NM_001034.4 | c.554A>G | p.Lys185Arg | missense_variant | 5/10 | ENST00000304567.10 | |
RRM2 | NM_001165931.1 | c.734A>G | p.Lys245Arg | missense_variant | 5/10 | ||
RRM2 | NR_164157.1 | n.614A>G | non_coding_transcript_exon_variant | 5/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRM2 | ENST00000304567.10 | c.554A>G | p.Lys185Arg | missense_variant | 5/10 | 1 | NM_001034.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 22, 2024 | The c.734A>G (p.K245R) alteration is located in exon 5 (coding exon 5) of the RRM2 gene. This alteration results from a A to G substitution at nucleotide position 734, causing the lysine (K) at amino acid position 245 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D;.;.;D;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;.;.;N;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;.;N;N
REVEL
Uncertain
Sift
Benign
.;T;.;T;T
Sift4G
Benign
.;T;T;T;T
Polyphen
B;.;.;B;.
Vest4
0.74, 0.74, 0.74
MutPred
Loss of ubiquitination at K185 (P = 0.011);.;.;Loss of ubiquitination at K185 (P = 0.011);.;
MVP
0.56
MPC
1.6
ClinPred
D
GERP RS
Varity_R
gMVP
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