Variant chr7-76480525-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001102594.3(DTX2):c.16A>G(p.Ser6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,453,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DTX2
NM_001102594.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.355

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045098394).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX2	NM_001102594.3 linkuse as main transcript	c.16A>G	p.Ser6Gly	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.16A>G	p.Ser6Gly	missense_variant	3/11	1	NM_001102594.3	ENSP00000411986.2		Q86UW9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

242752

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131852

show subpopulations

Gnomad AFR exome

AF:

0.0000641

Gnomad AMR exome

AF:

0.0000892

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000551

AC:

AN:

1453050

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.0000907

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

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

Jul 07, 2024

The c.16A>G (p.S6G) alteration is located in exon 4 (coding exon 1) of the DTX2 gene. This alteration results from a A to G substitution at nucleotide position 16, causing the serine (S) at amino acid position 6 to be replaced by a glycine (G). 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

Benign

0.059

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.1

DANN

Benign

0.70

DEOGEN2

Benign

0.060

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.56

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

M_CAP

Benign

0.0043

MetaRNN

Benign

0.045

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

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

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.038

Sift

Benign

0.25

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

Sift4G

Benign

0.21

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

Polyphen

0.0010, 0.0

.;.;.;B;.;B;.;.;B;.;.;.;B

Vest4

0.18, 0.18, 0.18, 0.13

MutPred

0.21

Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);Loss of glycosylation at S6 (P = 0.0057);

MVP

0.37

MPC

0.25

ClinPred

0.11

GERP RS

-5.8

Varity_R

0.080

gMVP

0.38

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