rs4668669

Positions:

• chr2-10207892-C-T

Variant summary

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

The NR_164157.1(RRM2):​n.1479-2419C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,010 control chromosomes in the GnomAD database, including 498 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 0.050 (498 hom., cov: 32)
• Consequence: RRM2 NR_164157.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRM2	NR_164157.1	n.1479-2419C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM2	ENST00000381786.7	n.483-2419C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7555 AN: 151892 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.0384

Gnomad FIN AF: 0.000664

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0499 AC: 7583 AN: 152010 Hom.: 498 Cov.: 32 AF XY: 0.0501 AC XY: 3719 AN XY: 74278

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0421

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.0383

Gnomad4 FIN AF: 0.000664

Gnomad4 NFE AF: 0.00293

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0351 Hom.: 48

Bravo AF: 0.0586

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.59
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4668669; hg19: chr2-10348018;