Genetic Variant DTX2:p.Arg86Cys (chr7-76480765-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001102594.3(DTX2):c.256C>T(p.Arg86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 1,604,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

DTX2
NM_001102594.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Publications

0 publications found

Variant links:

Genes affected

DTX2 (HGNC:15973): (deltex E3 ubiquitin ligase 2) DTX2 functions as an E3 ubiquitin ligase (Takeyama et al., 2003 [PubMed 12670957]).[supplied by OMIM, Nov 2009]

DTX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102594.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DTX2	NM_001102594.3	MANE Select	c.256C>T	p.Arg86Cys	missense	Exon 3 of 11	NP_001096064.1	Q86UW9-1
DTX2	NM_001102595.3		c.256C>T	p.Arg86Cys	missense	Exon 2 of 10	NP_001096065.1	Q86UW9-1
DTX2	NM_020892.4		c.256C>T	p.Arg86Cys	missense	Exon 4 of 12	NP_065943.2	Q86UW9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DTX2	ENST00000430490.7	TSL:1 MANE Select	c.256C>T	p.Arg86Cys	missense	Exon 3 of 11	ENSP00000411986.2	Q86UW9-1
DTX2	ENST00000324432.9	TSL:1	c.256C>T	p.Arg86Cys	missense	Exon 4 of 12	ENSP00000322885.5	Q86UW9-1
DTX2	ENST00000413936.6	TSL:1	c.256C>T	p.Arg86Cys	missense	Exon 2 of 10	ENSP00000390218.2	Q86UW9-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000156

AC:

AN:

237154

AF XY:

0.0000773

show subpopulations

Gnomad AFR exome

AF:

0.0000673

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000501

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.000226

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000544

AC:

AN:

1452388

Hom.:

Cov.:

AF XY:

0.0000471

AC XY:

AN XY:

721666

show subpopulations

African (AFR)

AF:

0.0000603

AC:

AN:

33186

American (AMR)

AF:

0.00

AC:

AN:

43454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25570

East Asian (EAS)

AF:

0.000202

AC:

AN:

39512

South Asian (SAS)

AF:

0.0000819

AC:

AN:

85464

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

52994

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.0000434

AC:

AN:

1106756

Other (OTH)

AF:

0.000117

AC:

AN:

59876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.0000328

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000275

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000231

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

Uncertain

0.49

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.5

PhyloP100

3.6

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.42

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.94

MVP

0.84

MPC

1.1

ClinPred

0.46

GERP RS

5.5

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.59

gMVP

0.73

Mutation Taster

=60/40

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over