2-10124582-T-C

Position:

• chr2-10124582-T-C

Variant summary

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

The ENST00000304567.10(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 ENST00000304567.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.87).
• 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/exons	MANE	Protein	UniProt
RRM2	NM_001034.4	c.436-135T>C		intron_variant		ENST00000304567.10	NP_001025.1
RRM2	NM_001165931.1	c.616-135T>C		intron_variant			NP_001159403.1
RRM2	NR_164157.1	n.496-135T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000304567.10	c.436-135T>C		intron_variant		1	NM_001034.4	ENSP00000302955	P1

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

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.547

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

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.528

Alfa AF: 0.546 Hom.: 10340

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs6741290; hg19: chr2-10264709;