2-10122837-C-G

Position:

• chr2-10122837-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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=0.19785485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRM2	NM_001034.4	c.39C>G	p.Asp13Glu	missense_variant	1/10	ENST00000304567.10
RRM2	NM_001165931.1	c.219C>G	p.Asp73Glu	missense_variant	1/10
RRM2	NR_164157.1	n.99C>G		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM2	ENST00000304567.10	c.39C>G	p.Asp13Glu	missense_variant	1/10	1	NM_001034.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.219C>G (p.D73E) 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 219, causing the aspartic acid (D) at amino acid position 73 to be replaced by a glutamic acid (E). 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
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;.;.;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.72	.;.;T;T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.58	N;.;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.15	.;N;.;N
REVEL	Uncertain	0.37
Sift	Benign	0.25	.;T;.;T
Sift4G	Benign	0.30	.;T;T;T
Polyphen		0.0	B;.;.;B
Vest4		0.027, 0.022, 0.045
MutPred		0.15		Loss of helix (P = 0.1299);.;.;Loss of helix (P = 0.1299);
MVP		0.50
MPC		0.65
ClinPred		0.22	T
GERP RS		4.7
Varity_R		0.14
gMVP		0.053

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-10262964;