2-15591874-A-G

Position:

• chr2-15591874-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004939.3(DDX1):​c.-60A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,460,938 control chromosomes in the GnomAD database, including 296,658 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 0.69 (37431 hom., cov: 34)
  • Exomes 𝑓: 0.63 (259227 hom.)
• Consequence: DDX1 NM_004939.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX1	NM_004939.3	c.-60A>G		5_prime_UTR_variant	1/26	ENST00000233084.8	NP_004930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX1	ENST00000233084.8	c.-60A>G		5_prime_UTR_variant	1/26	1	NM_004939.3	ENSP00000233084	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105014 AN: 152008 Hom.: 37389 Cov.: 34

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.625 AC: 818064 AN: 1308812 Hom.: 259227 Cov.: 28 AF XY: 0.628 AC XY: 403858 AN XY: 643114

Gnomad4 AFR exome AF: 0.863

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.927

Gnomad4 SAS exome AF: 0.731

Gnomad4 FIN exome AF: 0.537

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.691 AC: 105114 AN: 152126 Hom.: 37431 Cov.: 34 AF XY: 0.690 AC XY: 51343 AN XY: 74380

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.657

Alfa AF: 0.528 Hom.: 1574

Bravo AF: 0.708

Asia WGS AF: 0.837 AC: 2908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.6
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs10221770; hg19: chr2-15731998;