NM_006773.4:c.370+164C>T

Variant names:

• chr2-117817892-C-T
• rs6737733
• NM_006773.4:c.370+164C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDX18	NM_006773.4	c.370+164C>T		intron_variant	Intron 2 of 13	ENST00000263239.7	NP_006764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX18	ENST00000263239.7	c.370+164C>T		intron_variant	Intron 2 of 13	1	NM_006773.4	ENSP00000263239.2
DDX18	ENST00000474694.1	n.356+164C>T		intron_variant	Intron 3 of 8	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

African (AFR) AF: 0.476 AC: 19731 AN: 41426

American (AMR) AF: 0.259 AC: 3951 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1247 AN: 3470

East Asian (EAS) AF: 0.147 AC: 761 AN: 5164

South Asian (SAS) AF: 0.408 AC: 1965 AN: 4814

European-Finnish (FIN) AF: 0.217 AC: 2293 AN: 10544

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21236 AN: 67932

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.326 Hom.: 4756

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
PhyloP100		-4.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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