Genetic Variant DTX2:p.Arg53Cys (chr7-76480666-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001102594.3(DTX2):c.157C>T(p.Arg53Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,386 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: 0.0000089 ( 0 hom. )

Consequence

DTX2
NM_001102594.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2631656).

BS2

High AC in GnomAdExome4 at 13 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.157C>T	p.Arg53Cys	missense	Exon 3 of 11	NP_001096064.1	Q86UW9-1
DTX2	NM_001102595.3		c.157C>T	p.Arg53Cys	missense	Exon 2 of 10	NP_001096065.1	Q86UW9-1
DTX2	NM_020892.4		c.157C>T	p.Arg53Cys	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.157C>T	p.Arg53Cys	missense	Exon 3 of 11	ENSP00000411986.2	Q86UW9-1
DTX2	ENST00000324432.9	TSL:1	c.157C>T	p.Arg53Cys	missense	Exon 4 of 12	ENSP00000322885.5	Q86UW9-1
DTX2	ENST00000413936.6	TSL:1	c.157C>T	p.Arg53Cys	missense	Exon 2 of 10	ENSP00000390218.2	Q86UW9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

247698

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461386

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.0000447

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111848

Other (OTH)

AF:

0.0000166

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000247

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

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.16

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

M_CAP

Benign

0.031

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

PhyloP100

3.3

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.15

Sift

Uncertain

0.025

Sift4G

Benign

0.069

Polyphen

0.24

Vest4

0.66

MutPred

0.56

Loss of disorder (P = 0.0165)

MVP

0.64

MPC

0.41

ClinPred

0.77

GERP RS

4.8

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.16

gMVP

0.42

Mutation Taster

=84/16

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