NM_025132.4(WDR19):c.781dup (p.Thr261fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 4, 2024
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:: RCV001231474.5

Allele description [Variation Report for NM_025132.4(WDR19):c.781dup (p.Thr261fs)]

NM_025132.4(WDR19):c.781dup (p.Thr261fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

4p14

Genomic location:

Preferred name:

NM_025132.4(WDR19):c.781dup (p.Thr261fs)

HGVS:

NC_000004.11:g.39207246_39207247insA
NC_000004.12:g.39205627dup
NG_031813.1:g.28224dup
NM_001317924.2:c.301dup
NM_025132.4:c.781dupMANE SELECT
NP_001304853.1:p.Thr101fs
NP_079408.3:p.Thr261fs
NC_000004.11:g.39207246_39207247insA
NC_000004.11:g.39207247dup
NC_000004.11:g.39207247dupA
NC_000004.12:g.39205627_39205628insA
NM_025132.3:c.781dup
NM_025132.3:c.781dupA

Protein change:

T101fs

Links:

dbSNP: rs748656635

NCBI 1000 Genomes Browser:

rs748656635

Molecular consequence:

NM_001317924.2:c.301dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_025132.4:c.781dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001403998	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 4, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 22019273, 23559409, 23683095, 26275793, 27241786, 28973083, 29068549, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001403998

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 4, 2024)

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

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

Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with a nephronophthisis-related ciliopathy.

Halbritter J, Porath JD, Diaz KA, Braun DA, Kohl S, Chaki M, Allen SJ, Soliman NA, Hildebrandt F, Otto EA; GPN Study Group..

Hum Genet. 2013 Aug;132(8):865-84. doi: 10.1007/s00439-013-1297-0. Epub 2013 Apr 5.

PubMed [citation]

PMID:: 23559409
PMCID:: PMC4643834

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001403998.5

#	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 creates a premature translational stop signal (p.Thr261Asnfs*13) in the WDR19 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WDR19 are known to be pathogenic (PMID: 22019273, 23559409, 23683095, 26275793, 27241786, 29068549). This variant is present in population databases (rs748656635, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with asphyxiating thoracic dystrophy (PMID: 28973083, 29068549). ClinVar contains an entry for this variant (Variation ID: 446634). For these reasons, this variant has been classified as Pathogenic.

#	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: Jun 23, 2024

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