2-15617990-A-G

Variant names:

• chr2-15617990-A-G
• rs4668944
• NM_004939.3:c.1117-191A>G

Variant summary

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

The NM_004939.3(DDX1):​c.1117-191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,080 control chromosomes in the GnomAD database, including 34,514 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 0.66 (34514 hom., cov: 33)
• Consequence: DDX1 NM_004939.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 2 publications found

Genes affected

DDX1 (HGNC:2734): (DEAD-box helicase 1) 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 that acts as an ATP-dependent RNA helicase that has been found to promote coronaviruses replication. [provided by RefSeq, Aug 2021]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004939.3. 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
	DDX1	NM_004939.3	MANE Select	c.1117-191A>G		intron	N/A	NP_004930.1	Q92499-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX1	ENST00000233084.8	TSL:1 MANE Select	c.1117-191A>G		intron	N/A	ENSP00000233084.3	Q92499-1
	DDX1	ENST00000617198.5	TSL:1	c.841-191A>G		intron	N/A	ENSP00000482416.2	A0A087WZ71
	DDX1	ENST00000381341.7	TSL:5	c.1117-191A>G		intron	N/A	ENSP00000370745.1	Q92499-1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100834 AN: 151962 Hom.: 34479 Cov.: 33

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.664 AC: 100931 AN: 152080 Hom.: 34514 Cov.: 33 AF XY: 0.664 AC XY: 49383 AN XY: 74318

African (AFR) AF: 0.811 AC: 33674 AN: 41534

American (AMR) AF: 0.660 AC: 10080 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3470

East Asian (EAS) AF: 0.886 AC: 4585 AN: 5174

South Asian (SAS) AF: 0.752 AC: 3630 AN: 4826

European-Finnish (FIN) AF: 0.538 AC: 5682 AN: 10556

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39200 AN: 67932

Other (OTH) AF: 0.628 AC: 1326 AN: 2112

Alfa AF: 0.595 Hom.: 29239

Bravo AF: 0.678

Asia WGS AF: 0.827 AC: 2864 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.74
PhyloP100		-0.11
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: rs4668944; hg19: chr2-15758114;