NM_025132.4(WDR19):c.817A>G (p.Asn273Asp) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jul 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001204687.2

Allele description [Variation Report for NM_025132.4(WDR19):c.817A>G (p.Asn273Asp)]

NM_025132.4(WDR19):c.817A>G (p.Asn273Asp)

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.817A>G (p.Asn273Asp)
HGVS:
  • NC_000004.12:g.39205663A>G
  • NG_031813.1:g.28260A>G
  • NM_001317924.2:c.337A>G
  • NM_025132.4:c.817A>GMANE SELECT
  • NP_001304853.1:p.Asn113Asp
  • NP_079408.3:p.Asn273Asp
  • NC_000004.11:g.39207283A>G
  • NM_025132.3:c.817A>G
Protein change:
N113D
Links:
dbSNP: rs375644378
NCBI 1000 Genomes Browser:
rs375644378
Molecular consequence:
  • NM_001317924.2:c.337A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_025132.4:c.817A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Asphyxiating thoracic dystrophy 5 (SRTD5)
Synonyms:
SHORT-RIB THORACIC DYSPLASIA 5 WITH OR 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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001375904Invitaecriteria provided, single submitter
Uncertain significance
(Jul 27, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001375904.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces asparagine with aspartic acid at codon 273 of the WDR19 protein (p.Asn273Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs375644378, ExAC 0.004%). This variant has been observed in individuals affected with asphyxiating thoracic dystrophy (PMID: 29068549). ClinVar contains an entry for this variant (Variation ID: 446633). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 12, 2021

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