rs4669550

Positions:

• chr2-10182713-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641498.1(RRM2):​c.*115-15879A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,158 control chromosomes in the GnomAD database, including 3,705 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 0.21 (3705 hom., cov: 32)
• Consequence: RRM2 ENST00000641498.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRM2	NR_164157.1	n.1300-15879A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000641498.1	c.*115-15879A>G		intron_variant, NMD_transcript_variant				ENSP00000493425
RRM2	ENST00000381786.7	n.483-27598A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31970 AN: 152040 Hom.: 3700 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 32004 AN: 152158 Hom.: 3705 Cov.: 32 AF XY: 0.215 AC XY: 16026 AN XY: 74382

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.217

Alfa AF: 0.201 Hom.: 708

Bravo AF: 0.219

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.21
DANN	Benign	0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4669550; hg19: chr2-10322839;