NM_025132.4(WDR19):c.880G>A (p.Gly294Arg) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 3, 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:: RCV001851417.6

Allele description [Variation Report for NM_025132.4(WDR19):c.880G>A (p.Gly294Arg)]

NM_025132.4(WDR19):c.880G>A (p.Gly294Arg)

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.880G>A (p.Gly294Arg)

HGVS:

NC_000004.12:g.39205726G>A
NG_031813.1:g.28323G>A
NM_001317924.2:c.400G>A
NM_025132.4:c.880G>AMANE SELECT
NP_001304853.1:p.Gly134Arg
NP_079408.3:p.Gly294Arg
NC_000004.11:g.39207346G>A
NM_025132.3:c.880G>A

Protein change:

G134R

Links:

dbSNP: rs377160857

NCBI 1000 Genomes Browser:

rs377160857

Molecular consequence:

NM_001317924.2:c.400G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_025132.4:c.880G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002252087	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 3, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26275793, 29068549, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002252087

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 3, 2022)

germline

clinical testing

PubMed (3)
[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

Reproductive genetic counseling challenges associated with diagnostic exome sequencing in a large academic private reproductive genetic counseling practice.

Westerfield LE, Stover SR, Mathur VS, Nassef SA, Carter TG, Yang Y, Eng CM, Van den Veyver IB.

Prenat Diagn. 2015 Oct;35(10):1022-9. doi: 10.1002/pd.4674. Epub 2015 Sep 4.

PubMed [citation]

PMID:: 26275793

Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies.

Zhang W, Taylor SP, Ennis HA, Forlenza KN, Duran I, Li B, Sanchez JAO, Nevarez L, Nickerson DA, Bamshad M; University of Washington Center for Mendelian Genomics, Lachman RS, Krakow D, Cohn DH.

Hum Mutat. 2018 Jan;39(1):152-166. doi: 10.1002/humu.23362. Epub 2017 Nov 6.

PubMed [citation]

PMID:: 29068549
PMCID:: PMC6198324

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002252087.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 294 of the WDR19 protein (p.Gly294Arg). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt WDR19 protein function. ClinVar contains an entry for this variant (Variation ID: 446635). This missense change has been observed in individual(s) with clinical features of WDR19-related conditions (PMID: 26275793, 29068549). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs377160857, gnomAD 0.007%).

#	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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