2-117821194-G-T

Variant names:

• chr2-117821194-G-T
• rs61748152
• NM_006773.4:c.548G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006773.4(DDX18):​c.548G>T​(p.Cys183Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. C183Y) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DDX18 NM_006773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06763941).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX18	NM_006773.4	MANE Select	c.548G>T	p.Cys183Phe	missense	Exon 4 of 14	NP_006764.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX18	ENST00000263239.7	TSL:1 MANE Select	c.548G>T	p.Cys183Phe	missense	Exon 4 of 14	ENSP00000263239.2	Q9NVP1
	DDX18	ENST00000898166.1		c.548G>T	p.Cys183Phe	missense	Exon 4 of 15	ENSP00000568225.1
	DDX18	ENST00000921666.1		c.548G>T	p.Cys183Phe	missense	Exon 4 of 14	ENSP00000591725.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454212 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723192

African (AFR) AF: 0.00 AC: 0 AN: 33246

American (AMR) AF: 0.00 AC: 0 AN: 43520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.00 AC: 0 AN: 84310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5502

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108912

Other (OTH) AF: 0.00 AC: 0 AN: 60032

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.2
DANN	Benign	0.62
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.24
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.047
Sift	Benign	0.033	D
Sift4G	Uncertain	0.041	D
Polyphen		0.017	B
Vest4		0.31
MutPred		0.54		Loss of helix (P = 0.1299)
MVP		0.082
MPC		0.23
ClinPred		0.034	T
GERP RS		-0.45
Varity_R		0.043
gMVP		0.30
Mutation Taster		=88/12	polymorphism

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: rs61748152; hg19: chr2-118578770;