rs2726920

Positions:

• chr11-108876497-A-G
• chr11-108876497-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004398.4(DDX10):​c.2304+24288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,052 control chromosomes in the GnomAD database, including 43,279 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43279 hom., cov: 32)
• Consequence: DDX10 NM_004398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX10	NM_004398.4	c.2304+24288A>G		intron_variant		ENST00000322536.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX10	ENST00000322536.8	c.2304+24288A>G		intron_variant		1	NM_004398.4	P2

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114142 AN: 151932 Hom.: 43231 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.772

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.751 AC: 114247 AN: 152052 Hom.: 43279 Cov.: 32 AF XY: 0.755 AC XY: 56149 AN XY: 74346

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.773

Alfa AF: 0.777 Hom.: 20600

Bravo AF: 0.743

Asia WGS AF: 0.768 AC: 2671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.73

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: rs2726920; hg19: chr11-108747224;