NM_012472.6(DNAAF11):c.574C>T (p.Gln192Ter) AND Ciliary dyskinesia, primary, 19

Clinical significance:Pathogenic (Last evaluated: Nov 2, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000033017.7

Allele description [Variation Report for NM_012472.6(DNAAF11):c.574C>T (p.Gln192Ter)]

NM_012472.6(DNAAF11):c.574C>T (p.Gln192Ter)

Gene:
DNAAF11:dynein axonemal assembly factor 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q24.22
Genomic location:
Preferred name:
NM_012472.6(DNAAF11):c.574C>T (p.Gln192Ter)
HGVS:
  • NC_000008.11:g.132632819G>A
  • NG_033068.1:g.47799C>T
  • NM_001321961.2:c.574C>T
  • NM_001321962.2:c.328C>T
  • NM_001321963.2:c.214C>T
  • NM_001321964.2:c.214C>T
  • NM_001321965.2:c.214C>T
  • NM_001321966.2:c.214C>T
  • NM_012472.6:c.574C>TMANE SELECT
  • NP_001308890.1:p.Gln192Ter
  • NP_001308891.1:p.Gln110Ter
  • NP_001308892.1:p.Gln72Ter
  • NP_001308893.1:p.Gln72Ter
  • NP_001308894.1:p.Gln72Ter
  • NP_001308895.1:p.Gln72Ter
  • NP_036604.2:p.Gln192Ter
  • NC_000008.10:g.133645065G>A
  • NM_012472.3:c.574C>T
  • NM_012472.4:c.574C>T
  • NR_073525.3:n.626C>T
Protein change:
Q110*; GLN192TER
Links:
OMIM: 614930.0002; dbSNP: rs141945265
NCBI 1000 Genomes Browser:
rs141945265
Molecular consequence:
  • NR_073525.3:n.626C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001321961.2:c.574C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001321962.2:c.328C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001321963.2:c.214C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001321964.2:c.214C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001321965.2:c.214C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001321966.2:c.214C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012472.6:c.574C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Ciliary dyskinesia, primary, 19 (CILD19)
Synonyms:
CILIARY DYSKINESIA, PRIMARY, 19, WITH OR WITHOUT SITUS INVERSUS
Identifiers:
MONDO: MONDO:0013979; MedGen: C3543826; Orphanet: 244; OMIM: 614935

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000056797OMIMno assertion criteria providedPathogenic
(Nov 2, 2012)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000086956GeneReviewsno assertion criteria providedpathologic
(Sep 15, 2011)
not providedcuration

SCV000836236Invitaecriteria provided, single submitter
Pathogenic
(Nov 2, 2018)
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
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providednot providednot providednot providednot providednot providednot providednot providedcuration

Citations

PubMed

Loss-of-function mutations in LRRC6, a gene essential for proper axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia.

Kott E, Duquesnoy P, Copin B, Legendre M, Dastot-Le Moal F, Montantin G, Jeanson L, Tamalet A, Papon JF, Siffroi JP, Rives N, Mitchell V, de Blic J, Coste A, Clement A, Escalier D, Touré A, Escudier E, Amselem S.

Am J Hum Genet. 2012 Nov 2;91(5):958-64. doi: 10.1016/j.ajhg.2012.10.003.

PubMed [citation]
PMID:
23122589
PMCID:
PMC3487148

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 OMIM, SCV000056797.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a European male with primary ciliary dyskinesia-19 (CILD19; 614935), Kott et al. (2012) identified compound heterozygosity for 2 truncating mutations in exon 5 of the LRRC6 gene: a 574C-T transition, resulting in a gln192-to-ter (Q193X) substitution, and a 1-bp duplication (576dupA; 614930.0003), resulting in a frameshift and premature termination (Glu193ArgfsTer4). The patient had a chronic sinopulmonary syndrome with asthenospermia and immotile cilia lacking the inner and outer dynein arms. LRRC6 was not detected in airway epithelial cells from this patient, whereas it was detected in controls. The findings were consistent with a loss-of-function pathogenic mechanism.

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

From GeneReviews, SCV000086956.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

From Invitae, SCV000836236.2

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

Description

This sequence change creates a premature translational stop signal (p.Gln192*) in the LRRC6 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs141945265, ExAC 0.003%). This variant has been reported in an individual affected with primary ciliary dyskinesia (PMID: 23122589). ClinVar contains an entry for this variant (Variation ID: 39795). Loss-of-function variants in LRRC6 are known to be pathogenic (PMID: 23122589). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Feb 6, 2021

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