2-10142258-A-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2
The ENST00000641498.1(RRM2):c.1122A>T(p.Gly374=) variant causes a synonymous, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,468,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 0 hom. )
Consequence
RRM2
ENST00000641498.1 synonymous, NMD_transcript
ENST00000641498.1 synonymous, NMD_transcript
Scores
3
Clinical Significance
Conservation
PhyloP100: 0.177
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP7
Synonymous conserved (PhyloP=0.177 with no splicing effect.
BS2
High AC in GnomAd4 at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRM2 | NR_164157.1 | n.1182A>T | non_coding_transcript_exon_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRM2 | ENST00000381786.7 | n.365A>T | non_coding_transcript_exon_variant | 3/4 | 2 | ||||
RRM2 | ENST00000641498.1 | c.1122A>T | p.Gly374= | synonymous_variant, NMD_transcript_variant | 11/12 | ||||
RRM2 | ENST00000646978.1 | c.162A>T | p.Gly54= | synonymous_variant, NMD_transcript_variant | 3/4 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152026Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000129 AC: 32AN: 249000Hom.: 0 AF XY: 0.000156 AC XY: 21AN XY: 134792
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GnomAD4 exome AF: 0.000310 AC: 408AN: 1315922Hom.: 0 Cov.: 32 AF XY: 0.000317 AC XY: 207AN XY: 652342
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GnomAD4 genome AF: 0.000171 AC: 26AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74368
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 19, 2021 | The c.76A>T (p.M26L) alteration is located in exon 2 (coding exon 2) of the C2orf48 gene. This alteration results from a A to T substitution at nucleotide position 76, causing the methionine (M) at amino acid position 26 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at