1-200644457-AATT-A

Variant names:

• chr1-200644457-AATT-A
• rs1571603072
• NM_001031725.6:c.1654_1656delAAT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_001031725.6(DDX59):​c.1654_1656delAAT​(p.Asn552del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000000687 in 1,456,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DDX59 NM_001031725.6 conservative_inframe_deletion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.97
• Publications: 0 publications found

Genes affected

DDX59 (HGNC:25360): (DEAD-box helicase 59) Predicted to enable RNA binding activity and RNA helicase activity. Predicted to be located in cytoplasm and nucleus. Predicted to be integral component of membrane. Implicated in orofaciodigital syndrome V. [provided by Alliance of Genome Resources, Apr 2022]

DDX59 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome V

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001031725.6. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 1-200644457-AATT-A is Pathogenic according to our data. Variant chr1-200644457-AATT-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 800916.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031725.6. 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
	DDX59	NM_001031725.6	MANE Select	c.1654_1656delAAT	p.Asn552del	conservative_inframe_deletion	Exon 8 of 8	NP_001026895.2	Q5T1V6-1
	DDX59	NM_001349799.3		c.1654_1656delAAT	p.Asn552del	conservative_inframe_deletion	Exon 8 of 8	NP_001336728.1	Q5T1V6-1
	DDX59	NM_001349800.3		c.1654_1656delAAT	p.Asn552del	conservative_inframe_deletion	Exon 8 of 8	NP_001336729.1	Q5T1V6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX59	ENST00000331314.11	TSL:1 MANE Select	c.1654_1656delAAT	p.Asn552del	conservative_inframe_deletion	Exon 8 of 8	ENSP00000330460.6	Q5T1V6-1
	DDX59	ENST00000936161.1		c.1654_1656delAAT	p.Asn552del	conservative_inframe_deletion	Exon 7 of 7	ENSP00000606220.1
	DDX59	ENST00000936162.1		c.1654_1656delAAT	p.Asn552del	conservative_inframe_deletion	Exon 8 of 8	ENSP00000606221.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456340 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 724444

African (AFR) AF: 0.0000301 AC: 1 AN: 33204

American (AMR) AF: 0.00 AC: 0 AN: 43978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39344

South Asian (SAS) AF: 0.00 AC: 0 AN: 85164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109422

Other (OTH) AF: 0.00 AC: 0 AN: 60140

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Orofaciodigital syndrome V (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0
Mutation Taster		=51/49	disease causing (ClinVar)

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: rs1571603072; hg19: chr1-200613585;