NM_001034.4:c.39C>G

Variant names:

• chr2-10122837-C-G
• rs1662689296
• NM_001034.4:c.39C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034.4(RRM2):​c.39C>G​(p.Asp13Glu) 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. 13/22 in silico tools predict 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.216
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19785485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM2	NM_001034.4	MANE Select	c.39C>G	p.Asp13Glu	missense	Exon 1 of 10	NP_001025.1	P31350-1
	RRM2	NM_001165931.1		c.219C>G	p.Asp73Glu	missense	Exon 1 of 10	NP_001159403.1	P31350-2
	RRM2	NR_164157.1		n.99C>G		non_coding_transcript_exon	Exon 1 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM2	ENST00000304567.10	TSL:1 MANE Select	c.39C>G	p.Asp13Glu	missense	Exon 1 of 10	ENSP00000302955.4	P31350-1
	RRM2	ENST00000360566.6	TSL:1	c.219C>G	p.Asp73Glu	missense	Exon 1 of 10	ENSP00000353770.2	P31350-2
	RRM2	ENST00000641198.1		c.39C>G	p.Asp13Glu	missense	Exon 2 of 11	ENSP00000493399.1	P31350-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.0060	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.58	N
PhyloP100		0.22
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.15	N
REVEL	Uncertain	0.37
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.027
MutPred		0.15		Loss of helix (P = 0.1299)
MVP		0.50
MPC		0.65
ClinPred		0.22	T
GERP RS		4.7
PromoterAI		0.022	Neutral
Varity_R		0.14
gMVP		0.053
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1662689296; hg19: chr2-10262964;