Variant 7-76480671-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001102594.3(DTX2):c.162T>G(p.Phe54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,613,604 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 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

DTX2
NM_001102594.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.71

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:

DTX2 (HGNC:):

DTX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.101786494).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX2	NM_001102594.3 linkuse as main transcript	c.162T>G	p.Phe54Leu	missense_variant	3/11	ENST00000430490.7	NP_001096064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX2	ENST00000430490.7 linkuse as main transcript	c.162T>G	p.Phe54Leu	missense_variant	3/11	1	NM_001102594.3	ENSP00000411986.2		Q86UW9-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152208

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000323

AC:

AN:

247596

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134338

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:

0.0000724

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000883

AC:

129

AN:

1461396

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727004

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:

0.000113

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74364

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.162T>G (p.F54L) alteration is located in exon 4 (coding exon 1) of the DTX2 gene. This alteration results from a T to G substitution at nucleotide position 162, causing the phenylalanine (F) at amino acid position 54 to be replaced by a leucine (L). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.0080

DANN

Benign

0.90

DEOGEN2

Benign

0.090

.;T;.;T;T;T;T;T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.78

T;.;T;.;T;.;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.10

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

.;L;.;L;.;.;L;.;.;L

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

D;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.099

Sift

Benign

0.055

T;T;D;T;T;T;T;T;T;T

Sift4G

Benign

0.44

T;T;T;T;T;T;T;T;T;T

Polyphen

0.98, 0.70

.;D;.;D;.;.;D;.;.;P

Vest4

0.22, 0.21, 0.22, 0.21

MutPred

0.33

Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);Gain of disorder (P = 0.1034);

MVP

0.29

MPC

0.62

ClinPred

0.52

GERP RS

-7.2

Varity_R

0.057

gMVP

0.32

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