2-10142258-A-C

Variant names:

• chr2-10142258-A-C
• rs138491641
• ENST00000381786.7:n.365A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000381786.7(RRM2):​n.365A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,315,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: RRM2 ENST00000381786.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 0 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.054).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381786.7. 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	NR_164157.1		n.1182A>C		non_coding_transcript_exon	Exon 11 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM2	ENST00000381786.7	TSL:2	n.365A>C		non_coding_transcript_exon	Exon 3 of 4
	RRM2	ENST00000641498.1		n.1122A>C		non_coding_transcript_exon	Exon 11 of 12	ENSP00000493425.1	A0A286YFD6
	RRM2	ENST00000646978.1		n.159A>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000496624.1	A0A2R8Y837

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 9 AN: 1315920 Hom.: 0 Cov.: 32 AF XY: 0.00000613 AC XY: 4 AN XY: 652342

African (AFR) AF: 0.00 AC: 0 AN: 29888

American (AMR) AF: 0.00 AC: 0 AN: 40122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21212

East Asian (EAS) AF: 0.00 AC: 0 AN: 25832

South Asian (SAS) AF: 0.00 AC: 0 AN: 84088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5042

European-Non Finnish (NFE) AF: 0.00000883 AC: 9 AN: 1018792

Other (OTH) AF: 0.00 AC: 0 AN: 51244

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138491641; hg19: chr2-10282385;