rs767691365

Variant names:

• chr2-117819744-A-T
• rs767691365
• NM_006773.4:c.466A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-117819744-A-T
• chr2-117819744-A-C
• chr2-117819744-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006773.4(DDX18):​c.466A>T​(p.Asn156Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,088 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DDX18 NM_006773.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0540
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08402932).

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.466A>T	p.Asn156Tyr	missense	Exon 3 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.466A>T	p.Asn156Tyr	missense	Exon 3 of 14	ENSP00000263239.2	Q9NVP1
	DDX18	ENST00000898166.1		c.466A>T	p.Asn156Tyr	missense	Exon 3 of 15	ENSP00000568225.1
	DDX18	ENST00000921666.1		c.466A>T	p.Asn156Tyr	missense	Exon 3 of 14	ENSP00000591725.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457088 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724698

African (AFR) AF: 0.00 AC: 0 AN: 33154

American (AMR) AF: 0.00 AC: 0 AN: 43894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.00 AC: 0 AN: 85036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110238

Other (OTH) AF: 0.0000166 AC: 1 AN: 60198

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.054
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.055
Sift	Benign	0.058	T
Sift4G	Uncertain	0.016	D
Polyphen		0.50	P
Vest4		0.30
MutPred		0.24		Gain of phosphorylation at N156 (P = 0.0152)
MVP		0.28
MPC		0.26
ClinPred		0.29	T
GERP RS		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.070
Mutation Taster		=97/3	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: rs767691365; hg19: chr2-118577320;