Genetic Variant UBXN2A:p.Ile192Val (chr2-23984821-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181713.4(UBXN2A):c.574A>G(p.Ile192Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. I192F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBXN2A
NM_181713.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.287

Publications

0 publications found

Variant links:

Genes affected

UBXN2A (HGNC:27265): (UBX domain protein 2A) Predicted to enable ubiquitin binding activity. Predicted to be involved in several processes, including autophagosome assembly; nuclear membrane reassembly; and proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to act upstream of or within cellular response to leukemia inhibitory factor; regulation of gene expression; and regulation of protein metabolic process. Predicted to be located in cis-Golgi network and endoplasmic reticulum. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBXN2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04487577).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181713.4. 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
	UBXN2A	NM_181713.4	MANE Select	c.574A>G	p.Ile192Val	missense	Exon 6 of 7	NP_859064.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBXN2A	ENST00000309033.5	TSL:1 MANE Select	c.574A>G	p.Ile192Val	missense	Exon 6 of 7	ENSP00000312107.4	P68543-1
UBXN2A	ENST00000446425.2	TSL:1	n.1036A>G		non_coding_transcript_exon	Exon 7 of 8
UBXN2A	ENST00000404924.5	TSL:2	c.574A>G	p.Ile192Val	missense	Exon 7 of 8	ENSP00000385525.1	P68543-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398134

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694726

show subpopulations

African (AFR)

AF:

0.0000350

AC:

AN:

28584

American (AMR)

AF:

0.00

AC:

AN:

26884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24196

East Asian (EAS)

AF:

0.00

AC:

AN:

35180

South Asian (SAS)

AF:

0.00

AC:

AN:

74446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1092734

Other (OTH)

AF:

0.00

AC:

AN:

57658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.34

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.044

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.56

M_CAP

Benign

0.0027

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.97

PhyloP100

-0.29

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.15

REVEL

Benign

0.048

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.039

MutPred

0.22

Loss of catalytic residue at I192 (P = 0.0327)

MVP

0.37

MPC

0.10

ClinPred

0.024

GERP RS

-7.7

Varity_R

0.014

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over