2-10122846-G-A

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

2

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]

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 UniProt
RRM2NM_001034.4 linkuse as main transcriptc.48G>A p.Gln16= synonymous_variant 1/10 ENST00000304567.10
RRM2NM_001165931.1 linkuse as main transcriptc.228G>A p.Gln76= synonymous_variant 1/10
RRM2NR_164157.1 linkuse as main transcriptn.108G>A non_coding_transcript_exon_variant 1/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RRM2ENST00000304567.10 linkuse as main transcriptc.48G>A p.Gln16= synonymous_variant 1/101 NM_001034.4 P1P31350-1

Frequencies

GnomAD3 genomes
AF:
0.00162
AC:
246
AN:
152216
Hom.:
0
Cov.:
33
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.:
0
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.:
4
Cov.:
35
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.:
0
Cov.:
33
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.:
0
Bravo
AF:
0.00143
Asia WGS
AF:
0.000289
AC:
1
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 submitterclinical testingInvitaeJan 22, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
15
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.

Other links and lift over

dbSNP: rs150889173; hg19: chr2-10262973; API