chr2-117817639-C-G

Variant names:

• chr2-117817639-C-G
• rs1052637
• NM_006773.4:c.281C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006773.4(DDX18):​c.281C>G​(p.Thr94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,613,352 control chromosomes in the GnomAD database, including 117,529 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.42 (14675 hom., cov: 33)
  • Exomes 𝑓: 0.37 (102854 hom.)
• Consequence: DDX18 NM_006773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463
• Publications: 39 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 (MetaRNN=2.5178924E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX18	NM_006773.4	MANE Select	c.281C>G	p.Thr94Ser	missense	Exon 2 of 14	NP_006764.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX18	ENST00000263239.7	TSL:1 MANE Select	c.281C>G	p.Thr94Ser	missense	Exon 2 of 14	ENSP00000263239.2
	DDX18	ENST00000898166.1		c.281C>G	p.Thr94Ser	missense	Exon 2 of 15	ENSP00000568225.1
	DDX18	ENST00000921666.1		c.281C>G	p.Thr94Ser	missense	Exon 2 of 14	ENSP00000591725.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64448 AN: 151878 Hom.: 14661 Cov.: 33

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.374 AC: 93733 AN: 250654 AF XY: 0.380

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.371 AC: 541740 AN: 1461354 Hom.: 102854 Cov.: 36 AF XY: 0.374 AC XY: 271573 AN XY: 726988

African (AFR) AF: 0.582 AC: 19477 AN: 33464

American (AMR) AF: 0.331 AC: 14809 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9916 AN: 26122

East Asian (EAS) AF: 0.159 AC: 6321 AN: 39666

South Asian (SAS) AF: 0.464 AC: 40000 AN: 86218

European-Finnish (FIN) AF: 0.375 AC: 20010 AN: 53408

Middle Eastern (MID) AF: 0.399 AC: 2299 AN: 5758

European-Non Finnish (NFE) AF: 0.366 AC: 406468 AN: 1111650

Other (OTH) AF: 0.372 AC: 22440 AN: 60364

GnomAD4 genome AF: 0.424 AC: 64512 AN: 151998 Hom.: 14675 Cov.: 33 AF XY: 0.424 AC XY: 31534 AN XY: 74288

African (AFR) AF: 0.582 AC: 24106 AN: 41446

American (AMR) AF: 0.374 AC: 5719 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1035 AN: 5180

South Asian (SAS) AF: 0.463 AC: 2231 AN: 4822

European-Finnish (FIN) AF: 0.359 AC: 3792 AN: 10558

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24805 AN: 67932

Other (OTH) AF: 0.376 AC: 793 AN: 2110

Alfa AF: 0.336 Hom.: 2834

Bravo AF: 0.424

TwinsUK AF: 0.369 AC: 1368

ALSPAC AF: 0.363 AC: 1400

ESP6500AA AF: 0.579 AC: 2550

ESP6500EA AF: 0.365 AC: 3143

ExAC AF: 0.382 AC: 46379

Asia WGS AF: 0.351 AC: 1226 AN: 3478

EpiCase AF: 0.357

EpiControl AF: 0.367

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.2
DANN	Benign	0.92
DEOGEN2	Benign	0.0087	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.46
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.12
Sift	Benign	0.26	T
Sift4G	Benign	0.76	T
Polyphen		0.020	B
Vest4		0.039
MutPred		0.042		Gain of phosphorylation at T94 (P = 0.0969)
MPC		0.15
ClinPred		0.0031	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.052
Mutation Taster		=99/1	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: rs1052637; hg19: chr2-118575215; COSMIC: COSV54305397; COSMIC: COSV54305397;