2-10122769-C-G

Variant names:

• chr2-10122769-C-G
• rs978772062
• ENST00000360566.6:c.151C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001165931.1(RRM2):​c.151C>G​(p.Leu51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RRM2 NM_001165931.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.663

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09365603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM2	NM_001034.4	c.-30C>G		5_prime_UTR_variant	Exon 1 of 10	ENST00000304567.10	NP_001025.1
RRM2	NM_001165931.1	c.151C>G	p.Leu51Val	missense_variant	Exon 1 of 10		NP_001159403.1
RRM2	NR_164157.1	n.31C>G		non_coding_transcript_exon_variant	Exon 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000304567	c.-30C>G		5_prime_UTR_variant	Exon 1 of 10	1	NM_001034.4	ENSP00000302955.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151C>G (p.L51V) alteration is located in exon 1 (coding exon 1) of the RRM2 gene. This alteration results from a C to G substitution at nucleotide position 151, causing the leucine (L) at amino acid position 51 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	3.1
DANN	Benign	0.71
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.28	.;T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Uncertain	-0.0053	T
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.010	N;.
REVEL	Benign	0.18
Sift	Benign	0.69	T;.
Sift4G	Uncertain	0.029	D;D
Vest4		0.048
MutPred		0.26		Gain of MoRF binding (P = 0.1005);Gain of MoRF binding (P = 0.1005);
MVP		0.48
MPC		0.72
ClinPred		0.043	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.055

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs978772062; hg19: chr2-10262896;