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NM_025000.4(DCAF17):c.436del (p.Ala147fs) AND Woodhouse-Sakati syndrome

Germline classification:
Pathogenic (8 submissions)
Last evaluated:
May 8, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000191077.24

Allele description [Variation Report for NM_025000.4(DCAF17):c.436del (p.Ala147fs)]

NM_025000.4(DCAF17):c.436del (p.Ala147fs)

Gene:
DCAF17:DDB1 and CUL4 associated factor 17 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q31.1
Genomic location:
Preferred name:
NM_025000.4(DCAF17):c.436del (p.Ala147fs)
HGVS:
  • NC_000002.12:g.171448795del
  • NG_013038.2:g.19545del
  • NM_001164821.2:c.436del
  • NM_025000.4:c.436delMANE SELECT
  • NP_001158293.1:p.Ala147fs
  • NP_079276.2:p.Ala147fs
  • NC_000002.11:g.172305305del
  • NM_001164821.2:c.436delC
  • NM_025000.3:c.436delC
  • NM_025000.4:c.436delCMANE SELECT
  • NP_079276.2:p.Ala147HisfsTer9
  • NR_028482.2:n.788del
Protein change:
A147fs
Links:
OMIM: 612515.0001; dbSNP: rs797045038
NCBI 1000 Genomes Browser:
rs797045038
Molecular consequence:
  • NM_001164821.2:c.436del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_025000.4:c.436del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_028482.2:n.788del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
2

Condition(s)

Name:
Woodhouse-Sakati syndrome
Synonyms:
Extrapyramidal disorder, progressive, with primary hypogonadism, mental retardation, and alopecia; Progressive extrapyramidal disorder with primary hypogonadism and alopecia; Woodhouse and Sakati syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009419; MedGen: C0342286; Orphanet: 3464; OMIM: 241080

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000020709OMIM
no assertion criteria provided
Pathogenic
(Dec 1, 2008)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000245470Baylor Genetics - Adult_WES
criteria provided, single submitter

(Yang et al. 2013)
Pathogenic
(Oct 24, 2014)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000247163Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(May 5, 2015)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000297808GeneReviews
no classification provided
not providedgermlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

SCV001132988Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
no assertion criteria provided
Pathogenic
(Aug 25, 2019)
germlineclinical testing

SCV001416367Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Aug 15, 2021)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002018146Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Dec 21, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003924291Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(May 8, 2023)
germlineresearch

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes11not providednot providedyesclinical testing, research
not providedgermlineunknown11not providednot providednot providedclinical testing, literature only
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A syndrome of hypogonadism, alopecia, diabetes mellitus, mental retardation, deafness, and ECG abnormalities.

Woodhouse NJ, Sakati NA.

J Med Genet. 1983 Jun;20(3):216-9.

PubMed [citation]
PMID:
6876115
PMCID:
PMC1049050

Clinical whole-exome sequencing for the diagnosis of mendelian disorders.

Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, et al.

N Engl J Med. 2013 Oct 17;369(16):1502-11. doi: 10.1056/NEJMoa1306555. Epub 2013 Oct 2.

PubMed [citation]
PMID:
24088041
PMCID:
PMC4211433
See all PubMed Citations (11)

Details of each submission

From OMIM, SCV000020709.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 7 affected members of 2 Saudi families with Woodhouse-Sakati syndrome (WDSKS; 241080), including 1 of the original families described by Woodhouse and Sakati (1983), Alazami et al. (2008) identified homozygosity for a 1-bp deletion (436delC) in exon 4 of the DCAF17 gene, predicted to cause a frameshift in the beta-isoform of the protein and result in premature termination. The authors stated that in the alpha-isoform, the 1-bp deletion was predicted to lie in the 5-prime UTR and was unlikely to be pathogenic. The mutation was subsequently identified in 6 additional Saudi families with the disorder, but not in 274 Saudi control chromosomes. SNP-based haplotype analysis confirmed a founder effect, and the deletion likely arose approximately 55 generations earlier.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics - Adult_WES, SCV000245470.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providedyesclinical testing
(GTR000508680.4)
PubMed (3)
2not provided1not providednot providedclinical testing
(GTR000508680.4)
PubMed (3)

Description

This variant has been previously reported as disease-causing and was found once in our laboratory homozygous in a 23-year-old male with diabetes, dystonia, coordination difficulties, thumb stiffening, ulnar deviation of the hand, hypernasal voice, hypothyroidism, hypogonadism, chronic facial and extremity edema and erythema, similarly affected sib (not tested). Variant pathogenic in recessive state; heterozygotes are carriers.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided
(GTR000508680.4)
1not provided1not provided
2germlineunknownnot providednot providednot provided
(GTR000508680.4)
1not provided1not provided

From Genetic Services Laboratory, University of Chicago, SCV000247163.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From GeneReviews, SCV000297808.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV001132988.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001416367.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Ala147Hisfs*9) in the DCAF17 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DCAF17 are known to be pathogenic (PMID: 19026396, 20507343). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individuals with Woodhouse-Sakati syndrome (PMID: 19026396, 24015686, 26664771). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 209146). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Revvity Omics, Revvity, SCV002018146.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV003924291.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024