ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.8440_8447del (p.Lys2813_Glu2814insTer) (rs755136231)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557657 SCV000624299 pathogenic Primary ciliary dyskinesia 2020-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2814*) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported as homozygous, heterozygous or biallelic with other pathogenic DNAH5 variants in individuals affected with primary ciliary dyskinesia (PMID: 11788826, 16627867, 22416021, 25186273). This variant is also known as p.Glu2814fs*1 in the literature. ClinVar contains an entry for this variant (Variation ID: 454808). Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 16627867, 11788826). For these reasons, this variant has been classified as Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000778751 SCV000915115 pathogenic Ciliary dyskinesia, primary, 3 2018-03-05 criteria provided, single submitter clinical testing The DNAH5 c.8440_8447delGAACCAAA (p.Glu2814Ter) frameshift variant has been reported in five individuals with primary ciliary dyskinesia, including in one who carried the variant in a homozygous state, in three who carried the variant in a compound heterozygous state, and in one who carried the variant in a heterozygous state where a second variant was not identified, and also in a heterozygous state in an unaffected parent of a patient (Olbrich et al. 2002; Hornef et al, 2006; Djakow et al. 2012; Raidt et al. 2014; Djakow et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.000063 in the European (non-Finnish) population from the Genome Aggregation Database. In respiratory epithelial cilia from an individual homozygous for the p.Glu2814Ter variant, expression of DNAH5 was observed at the ciliary base and the cilia were immotile, whereas expression of DNAH5 in controls was observed along the entire length of the axoneme (Fliegauf et al. 2005). Based on the evidence and due to the potential impact of frameshift variants, the p.Glu2814Ter variant is classified as pathogenic for primary ciliary dyskinesia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
UNC Molecular Genetics Laboratory,University of North Carolina at Chapel Hill RCV000557657 SCV001431731 pathogenic Primary ciliary dyskinesia 2019-03-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV000557657 SCV001452278 pathogenic Primary ciliary dyskinesia 2020-09-16 no assertion criteria provided clinical testing

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