2-171443558-CA-CAA

Variant names:

• chr2-171443558-C-CA
• rs879253799
• NM_025000.4:c.270dupA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_025000.4(DCAF17):​c.270dupA​(p.Cys91MetfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCAF17 NM_025000.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.07
• Publications: 3 publications found

Genes affected

DCAF17 (HGNC:25784): (DDB1 and CUL4 associated factor 17) This gene encodes a nuclear transmembrane protein that associates with cullin 4A/damaged DNA binding protein 1 ubiquitin ligase complex. Mutations in this gene are associated with Woodhouse-Sakati syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

DCAF17 Gene-Disease associations (from GenCC):

• Woodhouse-Sakati syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-171443558-C-CA is Pathogenic according to our data. Variant chr2-171443558-C-CA is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 632550.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025000.4. 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
	DCAF17	NM_025000.4	MANE Select	c.270dupA	p.Cys91MetfsTer28	frameshift	Exon 3 of 14	NP_079276.2	Q5H9S7-1
	DCAF17	NM_001164821.2		c.270dupA	p.Cys91MetfsTer28	frameshift	Exon 3 of 12	NP_001158293.1	F5H7W1
	DCAF17	NR_028482.2		n.622dupA		non_coding_transcript_exon	Exon 3 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	ENST00000375255.8	TSL:1 MANE Select	c.270dupA	p.Cys91MetfsTer28	frameshift	Exon 3 of 14	ENSP00000364404.3	Q5H9S7-1
	DCAF17	ENST00000966668.1		c.270dupA	p.Cys91MetfsTer26	frameshift	Exon 3 of 15	ENSP00000636727.1
	DCAF17	ENST00000907633.1		c.261dupA	p.Cys88MetfsTer28	frameshift	Exon 3 of 14	ENSP00000577692.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Woodhouse-Sakati syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=0/200	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: rs879253799; hg19: chr2-172300068;