Genetic Variant UBXN2B:p.Gln62Glu (chr8-58416949-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001077619.2(UBXN2B):c.184C>G(p.Gln62Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBXN2B
NM_001077619.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.22

Variant links:

Genes affected

UBXN2B (HGNC:27035): (UBX domain protein 2B) Predicted to enable ubiquitin binding activity. Involved in establishment of mitotic spindle orientation; negative regulation of protein localization to centrosome; and positive regulation of mitotic centrosome separation. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and spindle pole centrosome. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBXN2B 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=0.27019888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2 link	c.184C>G	p.Gln62Glu	missense_variant	Exon 2 of 8	ENST00000399598.7	NP_001071087.1	Q14CS0
UBXN2B	NM_001363181.1 link	c.184C>G	p.Gln62Glu	missense_variant	Exon 2 of 7		NP_001350110.1
UBXN2B	NM_001330535.2 link	c.184C>G	p.Gln62Glu	missense_variant	Exon 2 of 6		NP_001317464.1	Q14CS0E5RJ36
UBXN2B	NR_156456.1 link	n.209C>G		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN2B	ENST00000399598.7 link	c.184C>G	p.Gln62Glu	missense_variant	Exon 2 of 8	1	NM_001077619.2	ENSP00000382507.2		Q14CS0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000831

AC:

AN:

240782

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000486

AC:

AN:

1441638

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

716926

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:

0.00000636

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.184C>G (p.Q62E) alteration is located in exon 2 (coding exon 2) of the UBXN2B gene. This alteration results from a C to G substitution at nucleotide position 184, causing the glutamine (Q) at amino acid position 62 to be replaced by a glutamic acid (E). 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

0.070

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.16

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.046

D;.

Polyphen

0.29

B;.

Vest4

0.32

MutPred

0.21

Gain of glycosylation at P61 (P = 0.0668);Gain of glycosylation at P61 (P = 0.0668);

MVP

0.71

MPC

0.11

ClinPred

0.72

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.55

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