Variant chr2-10122793-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001165931.1(RRM2):c.175T>G(p.Ser59Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,583,810 control chromosomes in the GnomAD database, including 409,250 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 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: 𝑓 0.75 ( 43577 hom., cov: 32)

Exomes 𝑓: 0.71 ( 365673 hom. )

Consequence

RRM2
NM_001165931.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

Variant links:

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]

RRM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.731291E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRM2	NM_001034.4 link	c.-6T>G		5_prime_UTR_variant	1/10	ENST00000304567.10	NP_001025.1	P31350-1
RRM2	NM_001165931.1 link	c.175T>G	p.Ser59Ala	missense_variant	1/10		NP_001159403.1	P31350-2
RRM2	NR_164157.1 link	n.55T>G		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000304567 link	c.-6T>G		5_prime_UTR_variant	1/10	1	NM_001034.4	ENSP00000302955.4		P31350-1

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113529

AN:

151998

Hom.:

43540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.904

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.748

GnomAD3 exomes

AF:

0.659

AC:

130679

AN:

198412

Hom.:

44744

AF XY:

0.660

AC XY:

70622

AN XY:

107054

show subpopulations

Gnomad AFR exome

AF:

0.907

Gnomad AMR exome

AF:

0.535

Gnomad ASJ exome

AF:

0.687

Gnomad EAS exome

AF:

0.327

Gnomad SAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.729

Gnomad OTH exome

AF:

0.683

GnomAD4 exome

AF:

0.710

AC:

1016035

AN:

1431694

Hom.:

365673

Cov.:

AF XY:

0.706

AC XY:

500808

AN XY:

709300

show subpopulations

Gnomad4 AFR exome

AF:

0.910

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.682

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.596

Gnomad4 FIN exome

AF:

0.717

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.701

GnomAD4 genome

AF:

0.747

AC:

113617

AN:

152116

Hom.:

43577

Cov.:

AF XY:

0.739

AC XY:

54965

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.904

Gnomad4 AMR

AF:

0.622

Gnomad4 ASJ

AF:

0.671

Gnomad4 EAS

AF:

0.338

Gnomad4 SAS

AF:

0.581

Gnomad4 FIN

AF:

0.732

Gnomad4 NFE

AF:

0.728

Gnomad4 OTH

AF:

0.748

Alfa

AF:

0.722

Hom.:

56699

Bravo

AF:

0.745

TwinsUK

AF:

0.733

AC:

2718

ALSPAC

AF:

0.743

AC:

2865

ESP6500AA

AF:

0.891

AC:

3831

ESP6500EA

AF:

0.714

AC:

6080

ExAC

AF:

0.632

AC:

73516

Asia WGS

AF:

0.508

AC:

1767

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

2.9

DANN

Benign

0.76

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.095

.;T

MetaRNN

Benign

8.7e-7

T;T

MetaSVM

Benign

-0.90

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.21

N;.

REVEL

Benign

0.21

Sift

Benign

1.0

T;.

Sift4G

Benign

0.15

T;T

Vest4

0.010

MPC

0.57

ClinPred

0.0061

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.042

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over