rs10929378

Variant names:

• chr2-15607269-C-T
• rs10929378
• NM_004939.3:c.912C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004939.3(DDX1):​c.912C>T​(p.Asn304Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,609,522 control chromosomes in the GnomAD database, including 301,706 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 (34087 hom., cov: 32)
  • Exomes 𝑓: 0.60 (267619 hom.)
• Consequence: DDX1 NM_004939.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• Publications: 26 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.7 with no splicing effect.
• 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.912C>T	p.Asn304Asn	synonymous	Exon 13 of 26	NP_004930.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX1	ENST00000233084.8	TSL:1 MANE Select	c.912C>T	p.Asn304Asn	synonymous	Exon 13 of 26	ENSP00000233084.3
	DDX1	ENST00000617198.5	TSL:1	c.636C>T	p.Asn212Asn	synonymous	Exon 11 of 24	ENSP00000482416.2
	DDX1	ENST00000381341.7	TSL:5	c.912C>T	p.Asn304Asn	synonymous	Exon 14 of 27	ENSP00000370745.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100103 AN: 151886 Hom.: 34051 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.622

GnomAD2 exomes AF: 0.640 AC: 160845 AN: 251326 AF XY: 0.634

Gnomad AFR exome AF: 0.817

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.886

Gnomad FIN exome AF: 0.532

Gnomad NFE exome AF: 0.570

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.600 AC: 875049 AN: 1457518 Hom.: 267619 Cov.: 35 AF XY: 0.603 AC XY: 437527 AN XY: 725336

African (AFR) AF: 0.816 AC: 27260 AN: 33410

American (AMR) AF: 0.669 AC: 29916 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 14931 AN: 26082

East Asian (EAS) AF: 0.916 AC: 36313 AN: 39664

South Asian (SAS) AF: 0.720 AC: 61990 AN: 86144

European-Finnish (FIN) AF: 0.532 AC: 28383 AN: 53392

Middle Eastern (MID) AF: 0.540 AC: 3111 AN: 5764

European-Non Finnish (NFE) AF: 0.574 AC: 635770 AN: 1108088

Other (OTH) AF: 0.620 AC: 37375 AN: 60260

GnomAD4 genome AF: 0.659 AC: 100201 AN: 152004 Hom.: 34087 Cov.: 32 AF XY: 0.660 AC XY: 49053 AN XY: 74306

African (AFR) AF: 0.809 AC: 33563 AN: 41476

American (AMR) AF: 0.657 AC: 10020 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2013 AN: 3466

East Asian (EAS) AF: 0.887 AC: 4582 AN: 5168

South Asian (SAS) AF: 0.747 AC: 3599 AN: 4818

European-Finnish (FIN) AF: 0.539 AC: 5681 AN: 10532

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38703 AN: 67966

Other (OTH) AF: 0.624 AC: 1319 AN: 2114

Alfa AF: 0.606 Hom.: 15119

Bravo AF: 0.673

Asia WGS AF: 0.828 AC: 2879 AN: 3478

EpiCase AF: 0.569

EpiControl AF: 0.563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.8
DANN	Benign	0.65
PhyloP100		0.70
Mutation Taster		=98/2	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: rs10929378; hg19: chr2-15747393;