rs368001878

Variant names:

• chr2-10122775-G-A
• ENST00000360566.6:c.157G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-10122775-G-A
• chr2-10122775-G-C
• chr2-10122775-G-T

Variant summary

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

The NM_001165931.1(RRM2):​c.157G>A​(p.Ala53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RRM2 NM_001165931.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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=0.10554266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM2	NM_001034.4	c.-24G>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000304567.10	NP_001025.1
RRM2	NM_001165931.1	c.157G>A	p.Ala53Thr	missense_variant	Exon 1 of 10		NP_001159403.1
RRM2	NR_164157.1	n.37G>A		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.-24G>A		5_prime_UTR_variant	Exon 1 of 10	1	NM_001034.4	ENSP00000302955.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416102 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 700146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	0.23
DANN	Uncertain	0.99
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.36	.;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Uncertain	0.17	D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.28	N;.
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.030	D;D
Vest4		0.055
MutPred		0.26		Loss of methylation at R56 (P = 0.0824);Loss of methylation at R56 (P = 0.0824);
MVP		0.33
MPC		0.70
ClinPred		0.18	T
GERP RS		0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.092

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: chr2-10262902;