Genetic Variant UBE2V2:p.Pro104Leu (chr8-48060701-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_003350.3(UBE2V2):c.311C>T(p.Pro104Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000462 in 1,515,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

UBE2V2
NM_003350.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42

Publications

1 publications found

Variant links:

Genes affected

UBE2V2 (HGNC:12495): (ubiquitin conjugating enzyme E2 V2) Ubiquitin-conjugating enzyme E2 variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein encoded by this gene also shares homology with ubiquitin-conjugating enzyme E2 variant 1 and yeast MMS2 gene product. It may be involved in the differentiation of monocytes and enterocytes. [provided by RefSeq, Jul 2008]

UBE2V2 links:

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ACMG classification

Classification was made for transcript

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_003350.3. 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
	UBE2V2	NM_003350.3	MANE Select	c.311C>T	p.Pro104Leu	missense	Exon 4 of 4	NP_003341.1	A0M8W4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBE2V2	ENST00000523111.7	TSL:1 MANE Select	c.311C>T	p.Pro104Leu	missense	Exon 4 of 4	ENSP00000428209.1	Q15819
UBE2V2	ENST00000520809.1	TSL:1	n.1581C>T		non_coding_transcript_exon	Exon 3 of 3
UBE2V2	ENST00000517630.5	TSL:4	c.191C>T	p.Pro64Leu	missense	Exon 4 of 4	ENSP00000429886.1	G3V113

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

197674

AF XY:

0.00000919

show subpopulations

Gnomad AFR exome

AF:

0.000174

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.33e-7

AC:

AN:

1363916

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676048

show subpopulations

African (AFR)

AF:

0.0000344

AC:

AN:

29030

American (AMR)

AF:

0.00

AC:

AN:

31800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23674

East Asian (EAS)

AF:

0.00

AC:

AN:

34254

South Asian (SAS)

AF:

0.00

AC:

AN:

68270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5424

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065066

Other (OTH)

AF:

0.00

AC:

AN:

55740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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

AF:

0.0000395

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2074

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

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

-0.0031

MutationAssessor

Uncertain

2.4

PhyloP100

7.4

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.32

Sift

Uncertain

0.013

Sift4G

Uncertain

0.048

Polyphen

0.0010

Vest4

0.68

MVP

0.65

MPC

0.73

ClinPred

0.91

GERP RS

5.3

Varity_R

0.47

gMVP

0.59

Mutation Taster

=27/73

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over