11-108715890-A-G

Position:

chr11-108715890-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004398.4(DDX10):c.1334A>G(p.Glu445Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0061 in 1,513,250 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 29 hom. )

Consequence

DDX10
NM_004398.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.42

Variant links:

Genes affected

DDX10 (HGNC:2735): (DEAD-box helicase 10) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, and it may be involved in ribosome assembly. Fusion of this gene and the nucleoporin gene, NUP98, by inversion 11 (p15q22) chromosome translocation is found in the patients with de novo or therapy-related myeloid malignancies. [provided by RefSeq, Jul 2008]

DDX10 links:

LOC124902750 (HGNC:):

LOC124902750 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009814739).

BP6

Variant 11-108715890-A-G is Benign according to our data. Variant chr11-108715890-A-G is described in ClinVar as [Benign]. Clinvar id is 218632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108715890-A-G is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX10	NM_004398.4 linkuse as main transcript	c.1334A>G	p.Glu445Gly	missense_variant	11/18	ENST00000322536.8
LOC124902750	XR_007062881.1 linkuse as main transcript	n.13355-16313T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX10	ENST00000322536.8 linkuse as main transcript	c.1334A>G	p.Glu445Gly	missense_variant	11/18	1	NM_004398.4	P2

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

705

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00696

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00769

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00448

AC:

1061

AN:

237062

Hom.:

AF XY:

0.00455

AC XY:

584

AN XY:

128354

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.000848

Gnomad ASJ exome

AF:

0.00240

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.00642

Gnomad NFE exome

AF:

0.00709

Gnomad OTH exome

AF:

0.00584

GnomAD4 exome

AF:

0.00626

AC:

8520

AN:

1360926

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

4077

AN XY:

682100

show subpopulations

Gnomad4 AFR exome

AF:

0.000712

Gnomad4 AMR exome

AF:

0.000912

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00223

Gnomad4 FIN exome

AF:

0.00714

Gnomad4 NFE exome

AF:

0.00727

Gnomad4 OTH exome

AF:

0.00667

GnomAD4 genome

AF:

0.00463

AC:

705

AN:

152324

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

338

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00696

Gnomad4 NFE

AF:

0.00769

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00555

Hom.:

Bravo

AF:

0.00386

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000686

AC:

ESP6500EA

AF:

0.00619

AC:

ExAC

AF:

0.00472

AC:

573

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jun 05, 2015

- -

DDX10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.22

Sift

Benign

0.090

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.89

P;P

Vest4

0.58

MVP

0.70

MPC

0.40

ClinPred

0.020

GERP RS

6.0

Varity_R

0.24

gMVP

0.54

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

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