2-10128671-A-G

Variant names:

• chr2-10128671-A-G
• rs4668664
• NM_001034.4:c.799-177A>G

Variant summary

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

The NM_001034.4(RRM2):​c.799-177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,148 control chromosomes in the GnomAD database, including 43,427 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 0.74 (43427 hom., cov: 32)
• Consequence: RRM2 NM_001034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.66
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM2	NM_001034.4	MANE Select	c.799-177A>G		intron	N/A	NP_001025.1	P31350-1
	RRM2	NM_001165931.1		c.979-177A>G		intron	N/A	NP_001159403.1	P31350-2
	RRM2	NR_164157.1		n.859-177A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM2	ENST00000304567.10	TSL:1 MANE Select	c.799-177A>G		intron	N/A	ENSP00000302955.4	P31350-1
	RRM2	ENST00000360566.6	TSL:1	c.979-177A>G		intron	N/A	ENSP00000353770.2	P31350-2
	RRM2	ENST00000615152.5	TSL:1	c.649-177A>G		intron	N/A	ENSP00000484183.2	A0A7P0SBL1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113247 AN: 152030 Hom.: 43390 Cov.: 32

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.745 AC: 113334 AN: 152148 Hom.: 43427 Cov.: 32 AF XY: 0.734 AC XY: 54563 AN XY: 74374

African (AFR) AF: 0.899 AC: 37342 AN: 41532

American (AMR) AF: 0.632 AC: 9663 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2800 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1732 AN: 5166

South Asian (SAS) AF: 0.597 AC: 2880 AN: 4824

European-Finnish (FIN) AF: 0.642 AC: 6780 AN: 10568

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.730 AC: 49619 AN: 67986

Other (OTH) AF: 0.758 AC: 1601 AN: 2112

Alfa AF: 0.737 Hom.: 162187

Bravo AF: 0.750

Asia WGS AF: 0.509 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.38
DANN	Benign	0.47
PhyloP100		-5.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs4668664; hg19: chr2-10268798;