12-48831248-CTTGAGG-C

Variant names:

• chr12-48831248-CTTGAGG-C
• rs2137479865
• NM_004818.3:c.2127_2132delCCTCAA

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_004818.3(DDX23):​c.2127_2132delCCTCAA​(p.Asn709_Leu710del) 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 Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX23 NM_004818.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.40
• Publications: 0 publications found

Genes affected

DDX23 (HGNC:17347): (DEAD-box helicase 23) 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 is a component of the U5 snRNP complex; it may facilitate conformational changes in the spliceosome during nuclear pre-mRNA splicing. An alternatively spliced transcript variant has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

DDX23 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_004818.3.
• PP5: Variant 12-48831248-CTTGAGG-C is Pathogenic according to our data. Variant chr12-48831248-CTTGAGG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1313838.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004818.3. 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
	DDX23	NM_004818.3	MANE Select	c.2127_2132delCCTCAA	p.Asn709_Leu710del	disruptive_inframe_deletion	Exon 16 of 17	NP_004809.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX23	ENST00000308025.8	TSL:1 MANE Select	c.2127_2132delCCTCAA	p.Asn709_Leu710del	disruptive_inframe_deletion	Exon 16 of 17	ENSP00000310723.2	Q9BUQ8-1
	DDX23	ENST00000870156.1		c.2127_2132delCCTCAA	p.Asn709_Leu710del	disruptive_inframe_deletion	Exon 16 of 17	ENSP00000540215.1
	DDX23	ENST00000926598.1		c.2127_2132delCCTCAA	p.Asn709_Leu710del	disruptive_inframe_deletion	Exon 17 of 18	ENSP00000596657.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

Splicing

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

Other links and lift over

dbSNP: rs2137479865; hg19: chr12-49225031;