Variant 2-10122846-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001034.4(RRM2):c.48G>A(p.Gln16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,602,314 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 4 hom. )

Consequence

RRM2
NM_001034.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.197

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 2-10122846-G-A is Benign according to our data. Variant chr2-10122846-G-A is described in ClinVar as [Benign]. Clinvar id is 711013.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.197 with no splicing effect.

BS2

High AC in GnomAd4 at 246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RRM2	NM_001034.4 linkuse as main transcript	c.48G>A	p.Gln16=	synonymous_variant	1/10	ENST00000304567.10
RRM2	NM_001165931.1 linkuse as main transcript	c.228G>A	p.Gln76=	synonymous_variant	1/10
RRM2	NR_164157.1 linkuse as main transcript	n.108G>A		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM2	ENST00000304567.10 linkuse as main transcript	c.48G>A	p.Gln16=	synonymous_variant	1/10	1	NM_001034.4	P1	P31350-1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00183

AC:

406

AN:

222102

Hom.:

AF XY:

0.00175

AC XY:

212

AN XY:

121152

show subpopulations

Gnomad AFR exome

AF:

0.000151

Gnomad AMR exome

AF:

0.000402

Gnomad ASJ exome

AF:

0.000324

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000354

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.00284

Gnomad OTH exome

AF:

0.00238

GnomAD4 exome

AF:

0.00228

AC:

3312

AN:

1449980

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1583

AN XY:

720350

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000394

Gnomad4 ASJ exome

AF:

0.000427

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000404

Gnomad4 FIN exome

AF:

0.00539

Gnomad4 NFE exome

AF:

0.00257

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00161

AC:

246

AN:

152334

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00143

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.89

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over