2-10124582-T-C

Variant names:

• chr2-10124582-T-C
• rs6741290
• NM_001034.4:c.436-135T>C

Variant summary

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

The NM_001034.4(RRM2):​c.436-135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 945,494 control chromosomes in the GnomAD database, including 140,780 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 0.49 (19221 hom., cov: 33)
  • Exomes 𝑓: 0.55 (121559 hom.)
• Consequence: RRM2 NM_001034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM2	NM_001034.4	c.436-135T>C		intron_variant	Intron 4 of 9	ENST00000304567.10	NP_001025.1
RRM2	NM_001165931.1	c.616-135T>C		intron_variant	Intron 4 of 9		NP_001159403.1
RRM2	NR_164157.1	n.496-135T>C		intron_variant	Intron 4 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000304567.10	c.436-135T>C		intron_variant	Intron 4 of 9	1	NM_001034.4	ENSP00000302955.4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75273 AN: 152010 Hom.: 19219 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.549 AC: 435670 AN: 793366 Hom.: 121559 AF XY: 0.549 AC XY: 223783 AN XY: 407800

African (AFR) AF: 0.408 AC: 7451 AN: 18284

American (AMR) AF: 0.442 AC: 9546 AN: 21612

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 12761 AN: 19316

East Asian (EAS) AF: 0.350 AC: 11667 AN: 33348

South Asian (SAS) AF: 0.509 AC: 29220 AN: 57448

European-Finnish (FIN) AF: 0.417 AC: 15573 AN: 37334

Middle Eastern (MID) AF: 0.605 AC: 1683 AN: 2784

European-Non Finnish (NFE) AF: 0.578 AC: 327348 AN: 565892

Other (OTH) AF: 0.547 AC: 20421 AN: 37348

GnomAD4 genome AF: 0.495 AC: 75301 AN: 152128 Hom.: 19221 Cov.: 33 AF XY: 0.486 AC XY: 36149 AN XY: 74378

African (AFR) AF: 0.414 AC: 17186 AN: 41500

American (AMR) AF: 0.460 AC: 7033 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2242 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1730 AN: 5194

South Asian (SAS) AF: 0.494 AC: 2384 AN: 4824

European-Finnish (FIN) AF: 0.401 AC: 4238 AN: 10556

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38672 AN: 67984

Other (OTH) AF: 0.528 AC: 1115 AN: 2112

Alfa AF: 0.548 Hom.: 11570

Bravo AF: 0.494

Asia WGS AF: 0.408 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.063
DANN	Benign	0.32
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6741290; hg19: chr2-10264709;