7-44568504-A-G

Variant names:

• chr7-44568504-A-G
• rs217378
• NM_019082.4:c.1384-281T>C

Variant summary

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

The NM_019082.4(DDX56):​c.1384-281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,574 control chromosomes in the GnomAD database, including 24,612 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 0.57 (24612 hom., cov: 30)
• Consequence: DDX56 NM_019082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 9 publications found

Genes affected

DDX56 (HGNC:18193): (DEAD-box helicase 56) This gene encodes a member of the DEAD box protein family. 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. The protein encoded by this gene shows ATPase activity in the presence of polynucleotides and associates with nucleoplasmic 65S preribosomal particles. This gene may be involved in ribosome synthesis, most likely during assembly of the large 60S ribosomal subunit. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

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 (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX56	NM_019082.4	c.1384-281T>C		intron_variant	Intron 11 of 13	ENST00000258772.10	NP_061955.1
DDX56	NM_001257189.2	c.1264-281T>C		intron_variant	Intron 10 of 12		NP_001244118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX56	ENST00000258772.10	c.1384-281T>C		intron_variant	Intron 11 of 13	1	NM_019082.4	ENSP00000258772.5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86105 AN: 151454 Hom.: 24585 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.569 AC: 86179 AN: 151574 Hom.: 24612 Cov.: 30 AF XY: 0.565 AC XY: 41803 AN XY: 74042

African (AFR) AF: 0.607 AC: 25079 AN: 41322

American (AMR) AF: 0.567 AC: 8628 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2048 AN: 5104

South Asian (SAS) AF: 0.449 AC: 2155 AN: 4804

European-Finnish (FIN) AF: 0.542 AC: 5666 AN: 10456

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38505 AN: 67890

Other (OTH) AF: 0.588 AC: 1236 AN: 2102

Alfa AF: 0.568 Hom.: 4176

Bravo AF: 0.574

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.78
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs217378; hg19: chr7-44608103;