9-33817854-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017811.4(UBE2R2):​c.97G>A​(p.Val33Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

UBE2R2
NM_017811.4 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11
Variant links:
Genes affected
UBE2R2 (HGNC:19907): (ubiquitin conjugating enzyme E2 R2) Protein kinase CK2 is a ubiquitous and pleiotropic Ser/Thr protein kinase involved in cell growth and transformation. This gene encodes a protein similar to the E2 ubiquitin conjugating enzyme UBC3/CDC34. Studies suggest that CK2-dependent phosphorylation of this ubiquitin-conjugating enzyme functions by regulating beta-TrCP substrate recognition and induces its interaction with beta-TrCP, enhancing beta-catenin degradation. [provided by RefSeq, Jul 2008]
UBE2R2-AS1 (HGNC:49911): (UBE2R2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBE2R2NM_017811.4 linkuse as main transcriptc.97G>A p.Val33Met missense_variant 1/5 ENST00000263228.4
UBE2R2-AS1NR_170204.1 linkuse as main transcriptn.242+773C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE2R2ENST00000263228.4 linkuse as main transcriptc.97G>A p.Val33Met missense_variant 1/51 NM_017811.4 P1
UBE2R2-AS1ENST00000705030.1 linkuse as main transcriptn.108+773C>T intron_variant, non_coding_transcript_variant
UBE2R2-AS1ENST00000454429.2 linkuse as main transcriptn.169+773C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 13, 2023The c.97G>A (p.V33M) alteration is located in exon 1 (coding exon 1) of the UBE2R2 gene. This alteration results from a G to A substitution at nucleotide position 97, causing the valine (V) at amino acid position 33 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.87
D
M_CAP
Pathogenic
0.50
D
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.16
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.028
D
Polyphen
0.95
P
Vest4
0.46
MutPred
0.50
Loss of catalytic residue at V33 (P = 0.0284);
MVP
0.45
MPC
2.5
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.37
gMVP
0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-33817852; API