chr2-10128671-A-G

Position:

• chr2-10128671-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

RRM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRM2	NM_001034.4	c.799-177A>G		intron_variant		ENST00000304567.10	NP_001025.1
RRM2	NM_001165931.1	c.979-177A>G		intron_variant			NP_001159403.1
RRM2	NR_164157.1	n.859-177A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM2	ENST00000304567.10	c.799-177A>G		intron_variant		1	NM_001034.4	ENSP00000302955.4

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

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.758

Alfa AF: 0.735 Hom.: 69309

Bravo AF: 0.750

Asia WGS AF: 0.509 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.38
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs4668664; hg19: chr2-10268798;