rs6741290

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-10124582-T-A
• chr2-10124582-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001034.4(RRM2):​c.436-135T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000013 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM2	NM_001034.4	c.436-135T>A		intron_variant	Intron 4 of 9	ENST00000304567.10	NP_001025.1
RRM2	NM_001165931.1	c.616-135T>A		intron_variant	Intron 4 of 9		NP_001159403.1
RRM2	NR_164157.1	n.496-135T>A		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>A		intron_variant	Intron 4 of 9	1	NM_001034.4	ENSP00000302955.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000126 AC: 1 AN: 795652 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 408920

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18326

American (AMR) AF: 0.0000461 AC: 1 AN: 21680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 33392

South Asian (SAS) AF: 0.00 AC: 0 AN: 57562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2790

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 567716

Other (OTH) AF: 0.00 AC: 0 AN: 37436

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 11570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.051
DANN	Benign	0.27
PhyloP100		-1.4
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

Other links and lift over

dbSNP: rs6741290; hg19: chr2-10264709;