2-117821509-A-G

Position:

• chr2-117821509-A-G

Variant summary

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

The NM_006773.4(DDX18):​c.651-141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,084,898 control chromosomes in the GnomAD database, including 4,071 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 0.088 (629 hom., cov: 32)
  • Exomes 𝑓: 0.082 (3442 hom.)
• Consequence: DDX18 NM_006773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

Genes affected

DDX18 (HGNC:2741): (DEAD-box helicase 18) 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 is activated by Myc protein. [provided by RefSeq, Jul 2008]

DDX18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX18	NM_006773.4	c.651-141A>G		intron_variant		ENST00000263239.7	NP_006764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX18	ENST00000263239.7	c.651-141A>G		intron_variant		1	NM_006773.4	ENSP00000263239.2
DDX18	ENST00000474694.1	n.637-141A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13338 AN: 152192 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.0819 AC: 76373 AN: 932588 Hom.: 3442 AF XY: 0.0815 AC XY: 38326 AN XY: 470176

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0461

Gnomad4 ASJ exome AF: 0.0672

Gnomad4 EAS exome AF: 0.0000891

Gnomad4 SAS exome AF: 0.0675

Gnomad4 FIN exome AF: 0.0822

Gnomad4 NFE exome AF: 0.0873

Gnomad4 OTH exome AF: 0.0826

GnomAD4 genome AF: 0.0878 AC: 13374 AN: 152310 Hom.: 629 Cov.: 32 AF XY: 0.0858 AC XY: 6389 AN XY: 74480

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.0775

Gnomad4 NFE AF: 0.0878

Gnomad4 OTH AF: 0.0804

Alfa AF: 0.0845 Hom.: 738

Bravo AF: 0.0870

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.022
DANN	Benign	0.29

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: rs10490632; hg19: chr2-118579085;