dbSNP rs6759180: RRM2:c.570-439G>A (chr2-10126436-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001034.4(RRM2):c.570-439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 159,448 control chromosomes in the GnomAD database, including 43,742 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 42013 hom., cov: 32)

Exomes 𝑓: 0.67 ( 1729 hom. )

Consequence

RRM2
NM_001034.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RRM2	NM_001034.4 link	c.570-439G>A	intron_variant	Intron 5 of 9	ENST00000304567.10	NP_001025.1	P31350-1
RRM2	NM_001165931.1 link	c.750-439G>A	intron_variant	Intron 5 of 9		NP_001159403.1	P31350-2
RRM2	NR_164157.1 link	n.630-439G>A	intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000304567.10 link	c.570-439G>A		intron_variant	Intron 5 of 9	1	NM_001034.4	ENSP00000302955.4		P31350-1

Frequencies

GnomAD3 genomes

AF:

0.732

AC:

111289

AN:

152006

Hom.:

41971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.892

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.739

GnomAD4 exome

AF:

0.673

AC:

4926

AN:

7324

Hom.:

1729

AF XY:

0.669

AC XY:

2565

AN XY:

3834

show subpopulations

African (AFR)

AF:

0.911

AC:

153

AN:

168

American (AMR)

AF:

0.545

AC:

384

AN:

704

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

140

AN:

170

East Asian (EAS)

AF:

0.302

AC:

AN:

232

South Asian (SAS)

AF:

0.607

AC:

312

AN:

514

European-Finnish (FIN)

AF:

0.610

AC:

133

AN:

218

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.702

AC:

3494

AN:

4976

Other (OTH)

AF:

0.701

AC:

234

AN:

334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

166

250

333

416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.732

AC:

111381

AN:

152124

Hom.:

42013

Cov.:

AF XY:

0.721

AC XY:

53649

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.892

AC:

37046

AN:

41532

American (AMR)

AF:

0.619

AC:

9452

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.793

AC:

2750

AN:

3470

East Asian (EAS)

AF:

0.337

AC:

1741

AN:

5164

South Asian (SAS)

AF:

0.597

AC:

2880

AN:

4828

European-Finnish (FIN)

AF:

0.634

AC:

6693

AN:

10552

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48352

AN:

67996

Other (OTH)

AF:

0.739

AC:

1556

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1432

2864

4295

5727

7159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.718

Hom.:

65940

Bravo

AF:

0.736

Asia WGS

AF:

0.509

AC:

1771

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.32

(source)

DANN

Benign

0.78

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over