Genetic Variant UBR2:p.Gly53Arg (chr6-42573812-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363705.2(UBR2):c.157G>C(p.Gly53Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,148 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G53A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UBR2
NM_001363705.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.95

Publications

0 publications found

Variant links:

Genes affected

UBR2 (HGNC:21289): (ubiquitin protein ligase E3 component n-recognin 2) Enables leucine binding activity. Involved in cellular response to leucine and negative regulation of TOR signaling. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. Predicted to colocalize with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

UBR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21884489).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363705.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBR2	NM_001363705.2	MANE Select	c.157G>C	p.Gly53Arg	missense	Exon 2 of 47	NP_001350634.1	Q8IWV8-4
UBR2	NM_015255.3		c.157G>C	p.Gly53Arg	missense	Exon 2 of 47	NP_056070.1	Q8IWV8-1
UBR2	NM_001184801.2		c.157G>C	p.Gly53Arg	missense	Exon 2 of 12	NP_001171730.1	Q8IWV8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBR2	ENST00000372901.2	TSL:5 MANE Select	c.157G>C	p.Gly53Arg	missense	Exon 2 of 47	ENSP00000361992.1	Q8IWV8-4
UBR2	ENST00000372899.6	TSL:1	c.157G>C	p.Gly53Arg	missense	Exon 2 of 47	ENSP00000361990.1	Q8IWV8-1
UBR2	ENST00000372903.6	TSL:1	c.157G>C	p.Gly53Arg	missense	Exon 2 of 12	ENSP00000361994.2	Q8IWV8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461148

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111624

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

0.048

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.028

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.4

PhyloP100

4.9

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.64

REVEL

Benign

0.17

Sift

Benign

0.12

Sift4G

Uncertain

0.042

Polyphen

0.21

Vest4

0.39

MutPred

0.47

Gain of solvent accessibility (P = 0.0471)

MVP

0.36

MPC

0.49

ClinPred

0.59

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.67

Mutation Taster

=34/66

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over