rs3740596

chr10-68914422-A-G

Variant summary

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

The NM_024045.2(DDX50):c.1089+218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 152,258 control chromosomes in the GnomAD database, including 306 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 0.057 (306 hom., cov: 33)
• Consequence: DDX50 NM_024045.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

DDX50 (HGNC:17906): (DExD-box helicase 50) 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box enzyme that may be involved in ribosomal RNA synthesis or processing. This gene and DDX21, also called RH-II/GuA, have similar genomic structures and are in tandem orientation on chromosome 10, suggesting that the two genes arose by gene duplication in evolution. This gene has pseudogenes on chromosomes 2, 3 and 4. Alternative splicing of this gene generates multiple transcript variants, but the full length nature of all the other variants but one has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX50	NM_024045.2	c.1089+218A>G		intron_variant		ENST00000373585.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX50	ENST00000373585.8	c.1089+218A>G		intron_variant		1	NM_024045.2	P1
DDX50	ENST00000460470.1	n.296+218A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8740 AN: 152140 Hom.: 306 Cov.: 33

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0654

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

GnomAD4 genome AF: 0.0574 AC: 8744 AN: 152258 Hom.: 306 Cov.: 33 AF XY: 0.0574 AC XY: 4270 AN XY: 74434

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0647

Alfa AF: 0.0564 Hom.: 28

Bravo AF: 0.0545

Asia WGS AF: 0.0280 AC: 96 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.65

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: rs3740596; hg19: chr10-70674178;