chr11-108715890-A-G

Position:

• chr11-108715890-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (29 hom.)
• Consequence: DDX10 NM_004398.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.42

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]

LOC124902750 (HGNC:):

ACMG classification

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 [Likely_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	c.1334A>G	p.Glu445Gly	missense_variant	11/18	ENST00000322536.8
LOC124902750	XR_007062881.1	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	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.: 2 Cov.: 32

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.: 8 AF XY: 0.00455 AC XY: 584 AN XY: 128354

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.: 29 Cov.: 24 AF XY: 0.00598 AC XY: 4077 AN XY: 682100

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.: 2 Cov.: 32 AF XY: 0.00454 AC XY: 338 AN XY: 74492

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.: 0

Bravo AF: 0.00386

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.000686 AC: 3

ESP6500EA AF: 0.00619 AC: 53

ExAC AF: 0.00472 AC: 573

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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, criteria provided, single submitter

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0098	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
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	T
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

Other links and lift over

dbSNP: rs116953461; hg19: chr11-108586617; COSMIC: COSV100489612;