NM_016628.5(WAC):c.1470_1477del (p.Gln492fs) AND DeSanto-Shinawi syndrome due to WAC point mutation

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 12, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001001096.8

Allele description [Variation Report for NM_016628.5(WAC):c.1470_1477del (p.Gln492fs)]

NM_016628.5(WAC):c.1470_1477del (p.Gln492fs)

Gene:

WAC:WW domain containing adaptor with coiled-coil [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10p12.1

Genomic location:

Preferred name:

NM_016628.5(WAC):c.1470_1477del (p.Gln492fs)

HGVS:

NC_000010.11:g.28614599_28614606del
NG_046603.1:g.87012_87019del
NM_016628.5:c.1470_1477delMANE SELECT
NM_100264.3:c.1335_1342del
NM_100486.4:c.1161_1168del
NP_057712.2:p.Gln492fs
NP_567822.1:p.Gln447fs
NP_567823.1:p.Gln389fs
NC_000010.10:g.28903528_28903535del
NC_000010.10:g.28903528_28903535delGTCACAGT

Protein change:

Q389fs

Links:

dbSNP: rs1589247025

NCBI 1000 Genomes Browser:

rs1589247025

Molecular consequence:

NM_016628.5:c.1470_1477del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_100264.3:c.1335_1342del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_100486.4:c.1161_1168del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: DeSanto-Shinawi syndrome due to WAC point mutation (DESSH)
Synonyms:: DEVELOPMENTAL DELAY, BEHAVIORAL ABNORMALITIES, FACIAL DYSMORPHISM, AND OCULAR ABNORMALITIES; Facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to WAC point mutation
Identifiers:: MONDO: MONDO:0014741; MedGen: C5681129; Orphanet: 284169; OMIM: 616708

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001158231	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Feb 12, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001158231

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Feb 12, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158231.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The WAC c.1470_1477del; p.Gln492fs variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant, located in exon 11 out of 14, creates a frame shift starting at codon Gln492 resulting in a new reading frame and a premature STOP codon. All previously reported patients with Desanto-Shinawi syndrome had nonsense, framesfift, deletion or splice variants in the WAC gene (Varvagiannis 2017, Uehara 2018, Vanegas 2018), with several of these variants located after p.Gln492fs variant, in exons 12 and 13 of the WAC gene. Uehara et al. (2018) suggested haploinsufficiency as a likely pathogenic molecular mechanism. References: Uehara T et al. Three patients with DeSanto-Shinawi syndrome: Further phenotypic delineation. Am J Med Genet A. 2018 Jun;176(6):1335-1340. PMID: 29663678. Vanegas S et al. DeSanto-Shinawi Syndrome: First Case in South America. Mol Syndromol. 2018 May;9(3):154-158. PMID:29928181. Varvagiannis K et al. WAC-Related Intellectual Disability. 2017 Nov 30. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews (Internet). Seattle (WA): University of Washington, Seattle; 1993-2019. Available from http://www.ncbi.nlm.nih.gov/books/NBK465012/PMID: 29190062.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 30, 2024

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