9-33817854-G-A

Variant names:

• chr9-33817854-G-A
• NM_017811.4:c.97G>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.11

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)

ACMG classification

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 rank	MANE	Protein	UniProt
UBE2R2	NM_017811.4	c.97G>A	p.Val33Met	missense_variant	Exon 1 of 5	ENST00000263228.4	NP_060281.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2R2	ENST00000263228.4	c.97G>A	p.Val33Met	missense_variant	Exon 1 of 5	1	NM_017811.4	ENSP00000263228.3
UBE2R2-AS1	ENST00000454429.2	n.169+773C>T		intron_variant	Intron 1 of 3	5
UBE2R2-AS1	ENST00000705030.1	n.108+773C>T		intron_variant	Intron 1 of 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

Submissions by phenotype

not specified Uncertain:1

Oct 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 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
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;