rs1052637

chr2-117817639-C-Achr2-117817639-C-Gchr2-117817639-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006773.4(DDX18):c.281C>A(p.Thr94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T94S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DDX18 NM_006773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064835995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX18	NM_006773.4	c.281C>A	p.Thr94Asn	missense_variant	2/14	ENST00000263239.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX18	ENST00000263239.7	c.281C>A	p.Thr94Asn	missense_variant	2/14	1	NM_006773.4	P1
DDX18	ENST00000474694.1	n.267C>A		non_coding_transcript_exon_variant	3/9	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461528 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	5.1
Dann	Benign	0.94
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.98	P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.070
Sift	Benign	0.060	T
Sift4G	Benign	0.49	T
Polyphen		0.047	B
Vest4		0.13
MutPred		0.095		Loss of phosphorylation at T94 (P = 0.0522);
MVP		0.32
MPC		0.17
ClinPred		0.18	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.11

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: rs1052637; hg19: chr2-118575215;