rs6737733

chr2-117817892-C-T

Variant summary

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

The NM_006773.4(DDX18):c.370+164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,944 control chromosomes in the GnomAD database, including 9,817 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 0.34 (9817 hom., cov: 32)
• Consequence: DDX18 NM_006773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.60

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX18	NM_006773.4	c.370+164C>T		intron_variant		ENST00000263239.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX18	ENST00000263239.7	c.370+164C>T		intron_variant		1	NM_006773.4	P1
DDX18	ENST00000474694.1	n.356+164C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52322 AN: 151826 Hom.: 9809 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.345 AC: 52360 AN: 151944 Hom.: 9817 Cov.: 32 AF XY: 0.340 AC XY: 25279 AN XY: 74262

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.317

Alfa AF: 0.325 Hom.: 4274

Bravo AF: 0.346

Asia WGS AF: 0.283 AC: 987 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.032
Dann	Benign	0.42

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: rs6737733; hg19: chr2-118575468; COSMIC: COSV54306159; COSMIC: COSV54306159;