ClinVar Miner

Submissions for variant NM_178452.6(DNAAF1):c.1300_1322del (p.Gly434fs)

dbSNP: rs745495583
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000629460 SCV000750403 pathogenic Primary ciliary dyskinesia 2024-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly434Profs*4) in the DNAAF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAAF1 are known to be pathogenic (PMID: 19944400, 19944405). This variant is present in population databases (rs745495583, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 19944405). ClinVar contains an entry for this variant (Variation ID: 525404). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000629460 SCV002692478 pathogenic Primary ciliary dyskinesia 2021-08-24 criteria provided, single submitter clinical testing The c.1300_1322del23 pathogenic mutation, located in coding exon 8 of the DNAAF1 gene, results from a deletion of 23 nucleotides at nucleotide positions 1300 to 1322, causing a translational frameshift with a predicted alternate stop codon (p.G434Pfs*4). This alteration was detected along with another DNAAF1 translational frameshift mutation in an individual with primary ciliary dyskinesia (PCD) (Duquesnoy P et al. Am J Hum Genet, 2009 Dec;85:890-6). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics RCV002492940 SCV002802778 likely pathogenic Primary ciliary dyskinesia 13 2023-12-29 criteria provided, single submitter clinical testing
GeneDx RCV005255610 SCV005908745 pathogenic not provided 2024-10-08 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 19944400, 19944405, Carretero-Vilarroig2024[casereport], 27996046)
PreventionGenetics, part of Exact Sciences RCV003935743 SCV004751027 likely pathogenic DNAAF1-related disorder 2024-01-12 no assertion criteria provided clinical testing The DNAAF1 c.1300_1322del23 variant is predicted to result in a frameshift and premature protein termination (p.Gly434Profs*4). This variant has been reported with a second DNAAF1 variant in an individual with primary ciliary dyskinesia (Duquesnoy et al. 2009. PubMed ID: 19944405) and in the heterozygous state in an individual with testicular cancer (Litchfield et al. 2016. PubMed ID: 27996046). At PreventionGenetics, this variant has been detected in the homozygous state in individuals who received testing for ciliopathies (Internal Data). This variant is reported in 0.0062% of alleles in individuals of European (non-Finnish) descent in gnomAD. Frameshift variants in DNAAF1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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