2-10126436-G-A

Position:

• chr2-10126436-G-A

Variant summary

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

The NM_001034.4(RRM2):​c.570-439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 159,448 control chromosomes in the GnomAD database, including 43,742 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 0.73 (42013 hom., cov: 32)
  • Exomes 𝑓: 0.67 (1729 hom.)
• Consequence: RRM2 NM_001034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRM2	NM_001034.4	c.570-439G>A		intron_variant		ENST00000304567.10	NP_001025.1
RRM2	NM_001165931.1	c.750-439G>A		intron_variant			NP_001159403.1
RRM2	NR_164157.1	n.630-439G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000304567.10	c.570-439G>A		intron_variant		1	NM_001034.4	ENSP00000302955	P1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111289 AN: 152006 Hom.: 41971 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.739

GnomAD4 exome AF: 0.673 AC: 4926 AN: 7324 Hom.: 1729 AF XY: 0.669 AC XY: 2565 AN XY: 3834

Gnomad4 AFR exome AF: 0.911

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.824

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.702

Gnomad4 OTH exome AF: 0.701

GnomAD4 genome AF: 0.732 AC: 111381 AN: 152124 Hom.: 42013 Cov.: 32 AF XY: 0.721 AC XY: 53649 AN XY: 74358

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.739

Alfa AF: 0.713 Hom.: 51069

Bravo AF: 0.736

Asia WGS AF: 0.509 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.32
DANN	Benign	0.78

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: rs6759180; hg19: chr2-10266563;