NM_025132.4(WDR19):c.2129T>C (p.Leu710Ser) AND not provided

Clinical significance:Likely pathogenic

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001356848.1

Allele description [Variation Report for NM_025132.4(WDR19):c.2129T>C (p.Leu710Ser)]

NM_025132.4(WDR19):c.2129T>C (p.Leu710Ser)

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.2129T>C (p.Leu710Ser)
HGVS:
  • NC_000004.12:g.39231943T>C
  • NG_031813.1:g.54540T>C
  • NM_001317924.2:c.1649T>C
  • NM_025132.4:c.2129T>CMANE SELECT
  • NP_001304853.1:p.Leu550Ser
  • NP_079408.3:p.Leu710Ser
  • NC_000004.11:g.39233563T>C
  • NM_025132.3:c.2129T>C
  • Q8NEZ3:p.Leu710Ser
Protein change:
L550S; LEU710SER
Links:
UniProtKB: Q8NEZ3#VAR_067314; OMIM: 608151.0001; dbSNP: rs387906980
NCBI 1000 Genomes Browser:
rs387906980
Molecular consequence:
  • NM_001317924.2:c.1649T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_025132.4:c.2129T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001552119Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedLikely pathogenicunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001552119.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The WDR19 p.L710S variant was identified in the literature as a homozygous variant in 2 of 151 families (freq=0.013) with autosomal recessive Retinitis Pigmentosa from Quebec but was not found in 200 French-Canadian controls (Coussa_2013_PMID:23683095). The variant was also identified in two siblings with Sensenbrenner syndrome in the compound heterozygous state with a WDR19 p.R1103* variant with the p.L710S variant inherited from the unaffected father and the p.R1103* variant inherited from the unaffected mother; neither of these variants were identified in 422 controls (Bredrup_2011_PMID:22019273). The variant was identified in dbSNP (ID: rs387906980), ClinVar (classified as pathogenic by OMIM and GeneReviews) and LOVD 3.0 (classified as likely pathogenic). The variant was identified in control databases in 3 of 249208 chromosomes at a frequency of 0.00001204 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Latino in 1 of 34514 chromosomes (freq: 0.000029) and European (non-Finnish) in 2 of 112986 chromosomes (freq: 0.000018), but was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Leu550 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

Support Center