11-108665284-C-G

Position:

• chr11-108665284-C-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.131C>G​(p.Pro44Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00248 in 1,607,396 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (8 hom.)
• Consequence: DDX10 NM_004398.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.39

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007487476).
• BP6: Variant 11-108665284-C-G is Benign according to our data. Variant chr11-108665284-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 777859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX10	NM_004398.4	c.131C>G	p.Pro44Arg	missense_variant	1/18	ENST00000322536.8	NP_004389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX10	ENST00000322536.8	c.131C>G	p.Pro44Arg	missense_variant	1/18	1	NM_004398.4	ENSP00000314348.3

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 311 AN: 152246 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00212 AC: 517 AN: 243450 Hom.: 0 AF XY: 0.00205 AC XY: 270 AN XY: 131966

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.000992

Gnomad ASJ exome AF: 0.0153

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000339

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.00237

Gnomad OTH exome AF: 0.00290

GnomAD4 exome AF: 0.00252 AC: 3670 AN: 1455032 Hom.: 8 Cov.: 31 AF XY: 0.00247 AC XY: 1785 AN XY: 723784

Gnomad4 AFR exome AF: 0.000517

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000141

Gnomad4 FIN exome AF: 0.00159

Gnomad4 NFE exome AF: 0.00267

Gnomad4 OTH exome AF: 0.00279

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152364 Hom.: 3 Cov.: 32 AF XY: 0.00185 AC XY: 138 AN XY: 74508

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00332 Hom.: 0

Bravo AF: 0.00189

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.00196 AC: 238

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 29, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

DDX10-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

This variant is classified as 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	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.85	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.0075	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.11
Sift	Benign	0.076	T;T
Sift4G	Benign	0.23	T;T
Polyphen		1.0	D;D
Vest4		0.55
MVP		0.63
MPC		0.39
ClinPred		0.046	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.53

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

Other links and lift over

dbSNP: rs149622934; hg19: chr11-108536011;