2-10142258-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The ENST00000641498.1(RRM2):​c.1122A>T​(p.Gly374=) variant causes a synonymous, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,468,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

RRM2
ENST00000641498.1 synonymous, NMD_transcript

Scores

3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.177
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 -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP7
Synonymous conserved (PhyloP=0.177 with no splicing effect.
BS2
High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RRM2NR_164157.1 linkuse as main transcriptn.1182A>T non_coding_transcript_exon_variant 11/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RRM2ENST00000381786.7 linkuse as main transcriptn.365A>T non_coding_transcript_exon_variant 3/42
RRM2ENST00000641498.1 linkuse as main transcriptc.1122A>T p.Gly374= synonymous_variant, NMD_transcript_variant 11/12
RRM2ENST00000646978.1 linkuse as main transcriptc.162A>T p.Gly54= synonymous_variant, NMD_transcript_variant 3/4

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152026
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000129
AC:
32
AN:
249000
Hom.:
0
AF XY:
0.000156
AC XY:
21
AN XY:
134792
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000287
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000310
AC:
408
AN:
1315922
Hom.:
0
Cov.:
32
AF XY:
0.000317
AC XY:
207
AN XY:
652342
show subpopulations
Gnomad4 AFR exome
AF:
0.0000669
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:
0.000383
Gnomad4 OTH exome
AF:
0.000312
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000344
Hom.:
0
Bravo
AF:
0.000113
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 19, 2021The c.76A>T (p.M26L) alteration is located in exon 2 (coding exon 2) of the C2orf48 gene. This alteration results from a A to T substitution at nucleotide position 76, causing the methionine (M) at amino acid position 26 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_noAF
Benign
-0.92
CADD
Benign
3.7
DANN
Benign
0.51

Splicing

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: rs138491641; hg19: chr2-10282385; API