Variant 6-42592200-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001363705.2(UBR2):c.388G>A(p.Gly130Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,700 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UBR2
NM_001363705.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2900958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR2	NM_001363705.2 linkuse as main transcript	c.388G>A	p.Gly130Arg	missense_variant	3/47	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBR2	ENST00000372901.2 linkuse as main transcript	c.388G>A	p.Gly130Arg	missense_variant	3/47	5	NM_001363705.2	ENSP00000361992.1	Q8IWV8-4
UBR2	ENST00000372899.6 linkuse as main transcript	c.388G>A	p.Gly130Arg	missense_variant	3/47	1		ENSP00000361990.1	Q8IWV8-1
UBR2	ENST00000372903.6 linkuse as main transcript	c.388G>A	p.Gly130Arg	missense_variant	3/12	1		ENSP00000361994.2	Q8IWV8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445700

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719372

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000113

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 submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.388G>A (p.G130R) alteration is located in exon 3 (coding exon 3) of the UBR2 gene. This alteration results from a G to A substitution at nucleotide position 388, causing the glycine (G) at amino acid position 130 to be replaced by an arginine (R). 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

0.31

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

.;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.56

N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.31

N;N;N

REVEL

Uncertain

0.38

Sift

Benign

0.47

T;D;D

Sift4G

Benign

0.079

T;T;T

Polyphen

0.059

B;B;.

Vest4

0.54

MutPred

0.48

Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);

MVP

0.23

MPC

0.51

ClinPred

0.83

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over