ENST00000381786.7:n.483-2419C>T

Variant names:

• chr2-10207892-C-T
• rs4668669
• ENST00000381786.7:n.483-2419C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000381786.7(RRM2):​n.483-2419C>T variant causes a intron 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 ENST00000381786.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RRM2	NR_164157.1	n.1479-2419C>T		intron_variant	Intron 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000381786.7	n.483-2419C>T		intron_variant	Intron 3 of 3	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

African (AFR) AF: 0.151 AC: 6241 AN: 41414

American (AMR) AF: 0.0421 AC: 642 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3470

East Asian (EAS) AF: 0.0216 AC: 112 AN: 5176

South Asian (SAS) AF: 0.0383 AC: 184 AN: 4810

European-Finnish (FIN) AF: 0.000664 AC: 7 AN: 10546

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00293 AC: 199 AN: 68012

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

Alfa AF: 0.0257 Hom.: 389

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
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4668669; hg19: chr2-10348018;