ENST00000381786.7:n.483-27598A>G

Variant names:

• chr2-10182713-A-G
• rs4669550
• ENST00000381786.7:n.483-27598A>G

Variant summary

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

The ENST00000381786.7(RRM2):​n.483-27598A>G variant causes a intron 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 ENST00000381786.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26
• Publications: 2 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=-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 rank	MANE	Protein	UniProt
RRM2	NR_164157.1	n.1300-15879A>G		intron_variant	Intron 11 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000381786.7	n.483-27598A>G		intron_variant	Intron 3 of 3	2
RRM2	ENST00000641498.1	n.*115-15879A>G		intron_variant	Intron 11 of 11			ENSP00000493425.1

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

African (AFR) AF: 0.199 AC: 8279 AN: 41500

American (AMR) AF: 0.281 AC: 4297 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2661 AN: 5180

South Asian (SAS) AF: 0.275 AC: 1323 AN: 4816

European-Finnish (FIN) AF: 0.190 AC: 2013 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12062 AN: 68000

Other (OTH) AF: 0.217 AC: 457 AN: 2106

Alfa AF: 0.214 Hom.: 1491

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
PhyloP100		-3.3
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: rs4669550; hg19: chr2-10322839;