chr9-33817792-C-T

Variant names:

• chr9-33817792-C-T
• NM_017811.4:c.35C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017811.4(UBE2R2):​c.35C>T​(p.Ala12Val) 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: 6.90
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017811.4. 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
	UBE2R2	NM_017811.4	MANE Select	c.35C>T	p.Ala12Val	missense	Exon 1 of 5	NP_060281.2
	UBE2R2-AS1	NR_170201.1		n.242+835G>A		intron	N/A
	UBE2R2-AS1	NR_170202.1		n.242+835G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2R2	ENST00000263228.4	TSL:1 MANE Select	c.35C>T	p.Ala12Val	missense	Exon 1 of 5	ENSP00000263228.3	Q712K3
	UBE2R2	ENST00000878936.1		c.35C>T	p.Ala12Val	missense	Exon 1 of 5	ENSP00000548995.1
	UBE2R2	ENST00000878933.1		c.35C>T	p.Ala12Val	missense	Exon 1 of 4	ENSP00000548992.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.014
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PhyloP100		6.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.19
Sift	Benign	0.073	T
Sift4G	Benign	0.29	T
Polyphen		0.19	B
Vest4		0.56
MutPred		0.65		Gain of methylation at K11 (P = 0.0487)
MVP		0.53
MPC		2.4
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.54
gMVP		0.80
Mutation Taster		=39/61	disease causing

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

hg19: chr9-33817790;