NM_025132.4(WDR19):c.1479+2T>C AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 19, 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:: RCV001379131.5

Allele description [Variation Report for NM_025132.4(WDR19):c.1479+2T>C]

NM_025132.4(WDR19):c.1479+2T>C

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

4p14

Genomic location:

Preferred name:

NM_025132.4(WDR19):c.1479+2T>C

HGVS:

NC_000004.12:g.39218107T>C
NG_031813.1:g.40704T>C
NM_001317924.2:c.999+2T>C
NM_025132.4:c.1479+2T>CMANE SELECT
NC_000004.11:g.39219727T>C

Links:

dbSNP: rs756329385

NCBI 1000 Genomes Browser:

rs756329385

Molecular consequence:

NM_001317924.2:c.999+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_025132.4:c.1479+2T>C - 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

Recent activity

Clear Turn Off Turn On

Acinetobacter baumannii strain SQ081 contig_5497_len_237:location=plasmid, whole...
Acinetobacter baumannii strain SQ081 contig_5497_len_237:location=plasmid, whole genome shotgun sequence
gi|1938467160|ref|NZ_JADQAC01000032 gnl|WGS:NZ_JADQAC01|contig_5497_len_237:location=plasmid

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001576872	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 19, 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

SCV001576872

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 19, 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, SCV001576872.4

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

Description

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: 1067777). This variant has not been reported in the literature in individuals affected with WDR19-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects a donor splice site in intron 14 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).

#	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

ClinVar

Relating variation to medicine