NM_025132.4(WDR19):c.716+2del AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 13, 2022
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:: RCV001211083.6

Allele description [Variation Report for NM_025132.4(WDR19):c.716+2del]

NM_025132.4(WDR19):c.716+2del

Gene:

WDR19:WD repeat domain 19 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

4p14

Genomic location:

Preferred name:

NM_025132.4(WDR19):c.716+2del

HGVS:

NC_000004.12:g.39205268del
NG_031813.1:g.27865del
NM_001317924.2:c.236+2del
NM_025132.4:c.716+2delMANE SELECT
NC_000004.11:g.39206888del
NM_025132.3:c.716+2del

Links:

dbSNP: rs1727827349

NCBI 1000 Genomes Browser:

rs1727827349

Molecular consequence:

NM_001317924.2:c.236+2del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_025132.4:c.716+2del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Asphyxiating thoracic dystrophy 5 (SRTD5)
Synonyms:: SHORT-RIB THORACIC DYSPLASIA 5 WITH OR WITHOUT POLYDACTYLY; SHORT-RIB THORACIC DYSPLASIA 5 WITHOUT POLYDACTYLY
Identifiers:: MONDO: MONDO:0013717; MedGen: C3280598; Orphanet: 474; OMIM: 614376

Name:: Senior-Loken syndrome 8 (SLSN8)
Identifiers:: MONDO: MONDO:0014579; MedGen: C4225376; Orphanet: 3156; OMIM: 616307

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001382605	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 13, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16199547, 22019273, 23559409, 23683095, 26275793, 27241786, 29068549, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001382605

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 13, 2022)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19.

Bredrup C, Saunier S, Oud MM, Fiskerstrand T, Hoischen A, Brackman D, Leh SM, Midtbø M, Filhol E, Bole-Feysot C, Nitschké P, Gilissen C, Haugen OH, Sanders JS, Stolte-Dijkstra I, Mans DA, Steenbergen EJ, Hamel BC, Matignon M, Pfundt R, Jeanpierre C, Boman H, et al.

Am J Hum Genet. 2011 Nov 11;89(5):634-43. doi: 10.1016/j.ajhg.2011.10.001. Epub 2011 Oct 20.

PubMed [citation]

PMID:: 22019273
PMCID:: PMC3213394

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001382605.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change affects a splice site in intron 8 of the WDR19 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in WDR19 are known to be pathogenic (PMID: 22019273, 23559409, 23683095, 26275793, 27241786, 29068549). This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 941323). This variant has not been reported in the literature in individuals affected with WDR19-related conditions.

#	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: Sep 29, 2024

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