12-31091784-GCAGGAC-G

Variant names:

• chr12-31091784-GCAGGAC-G
• rs1057520059
• NM_030653.4:c.1160_1165delACCAGG

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_030653.4(DDX11):​c.1160_1165delACCAGG​(p.Asp387_Gln388del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: DDX11 NM_030653.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.08
• Publications: 0 publications found

Genes affected

DDX11 (HGNC:2736): (DEAD/H-box helicase 11) 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, which is an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

DDX11 Gene-Disease associations (from GenCC):

• Warsaw breakage syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_030653.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX11	NM_030653.4	MANE Select	c.1160_1165delACCAGG	p.Asp387_Gln388del	disruptive_inframe_deletion	Exon 10 of 27	NP_085911.2
	DDX11	NM_001257144.2		c.1160_1165delACCAGG	p.Asp387_Gln388del	disruptive_inframe_deletion	Exon 10 of 27	NP_001244073.1
	DDX11	NM_001413695.1		c.1160_1165delACCAGG	p.Asp387_Gln388del	disruptive_inframe_deletion	Exon 12 of 29	NP_001400624.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX11	ENST00000542838.6	TSL:1 MANE Select	c.1160_1165delACCAGG	p.Asp387_Gln388del	disruptive_inframe_deletion	Exon 10 of 27	ENSP00000443426.1
	DDX11	ENST00000545668.5	TSL:1	c.1160_1165delACCAGG	p.Asp387_Gln388del	disruptive_inframe_deletion	Exon 10 of 27	ENSP00000440402.1
	DDX11	ENST00000228264.10	TSL:1	c.1082_1087delACCAGG	p.Asp361_Gln362del	disruptive_inframe_deletion	Exon 10 of 27	ENSP00000228264.6

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 26, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1057520059; hg19: chr12-31244718;