ClinVar Miner

Submissions for variant NM_012472.6(DNAAF11):c.79_80del (p.Ser27fs) (rs769220870)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000650325 SCV000772168 pathogenic Ciliary dyskinesia, primary, 19 2019-02-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser27Valfs*13) in the LRRC6 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs769220870, ExAC 0.03%). This variant has been observed to be homozygous in multiple individuals affected with primary ciliary dyskinesia (Invitae). Loss-of-function variants in LRRC6 are known to be pathogenic (PMID: 23122589). For these reasons, this variant has been classified as Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000650325 SCV000916221 uncertain significance Ciliary dyskinesia, primary, 19 2017-04-28 criteria provided, single submitter clinical testing The LRRC6 c.79_80delTC (p.Ser27ValfsTer13) variant results in a frameshift and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. Based on this search no publications were found reporting the p.Ser27ValfsTer13 variant in association with primary ciliary dyskinesia, however the p.Ser27ValfsTer13 variant was reported in one study, segregating in an autosomal dominant manner across a father and son with testicular germ cell tumor (Litchfield et al. 2016). The p.Ser27ValfsTer13 was absent from 1644 UK population control subjects but is reported at a frequency of 0.004140 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the limited evidence, the frequency databases and the potential impact on protein expression, the LRRC6 is classified as a variant of unknown significance but suspicious for pathogenicity for primary ciliary dyskinesia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Columbia University Medical Center,Columbia University RCV000650325 SCV001478437 likely pathogenic Ciliary dyskinesia, primary, 19 2021-02-05 criteria provided, single submitter clinical testing Whole exome sequencing of the proband and parents identified heterozygous p.S27Vfs*13 variants in both the mother and father and the homozygous variant in the proband. The proband was found to have situs inversus and polysplenia at birth. The variant is present in the population at low level (gnomAD: 45/251288=0.000179). The p.S27Vfs*13 variant has been reported once as a homozygous variant in a patient with primary ciliary dyskinesia (Gileles-Hillel, 2020 (PMID: 33447612)). The proband is the product of a nonconsanguineous union between two parents of Ashkenazi Jewish descent with family histories negative for similarly affected individuals. While no functional data for this variant is available, in vitro studies of downstream truncating variants are recognized loss-of-function causes of autosomal recessive primary ciliary dyskinesia-19 (Kott 2012 (PMID: 23122589), Zariwala 2013 (PubMed: 23891469)).

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