rs16855939

Variant names:

• chr2-10170831-G-A
• rs16855939
• ENST00000381786.7:n.482+28456G>A

Variant summary

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

The ENST00000381786.7(RRM2):​n.482+28456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,240 control chromosomes in the GnomAD database, including 200 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 0.053 (200 hom., cov: 32)
• Consequence: RRM2 ENST00000381786.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM2	NR_164157.1	n.1300-27761G>A		intron_variant	Intron 11 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000381786.7	n.482+28456G>A		intron_variant	Intron 3 of 3	2
RRM2	ENST00000641498.1	n.*115-27761G>A		intron_variant	Intron 11 of 11			ENSP00000493425.1

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8023 AN: 152122 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0528 AC: 8032 AN: 152240 Hom.: 200 Cov.: 32 AF XY: 0.0528 AC XY: 3931 AN XY: 74440

African (AFR) AF: 0.0642 AC: 2667 AN: 41536

American (AMR) AF: 0.0626 AC: 958 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3470

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5174

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4828

European-Finnish (FIN) AF: 0.0376 AC: 399 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0457 AC: 3105 AN: 68000

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0509 Hom.: 252

Bravo AF: 0.0552

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.89
PhyloP100		-0.38
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: rs16855939; hg19: chr2-10310957;