ClinVar Miner

Submissions for variant NM_001010892.3(RSPH4A):c.1351C>T (p.Gln451Ter)

gnomAD frequency: 0.00005  dbSNP: rs750528020
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000539991 SCV000623954 pathogenic Primary ciliary dyskinesia 2023-10-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln451*) in the RSPH4A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RSPH4A are known to be pathogenic (PMID: 19200523). This variant is present in population databases (rs750528020, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 23993197). ClinVar contains an entry for this variant (Variation ID: 454520). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002497041 SCV002806180 pathogenic Primary ciliary dyskinesia 11 2022-04-07 criteria provided, single submitter clinical testing
NHS Central & South Genomic Laboratory Hub RCV004782426 SCV005393982 pathogenic Respiratory ciliopathies including non-CF bronchiectasis 2024-11-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000539991 SCV005489336 pathogenic Primary ciliary dyskinesia 2024-07-10 criteria provided, single submitter clinical testing The p.Q451* pathogenic mutation (also known as c.1351C>T), located in coding exon 3 of the RSPH4A gene, results from a C to T substitution at nucleotide position 1351. This changes the amino acid from a glutamine to a stop codon within coding exon 3. This variant has been identified in conjunction with another RSPH4A variant in an individual with features consistent with primary ciliary dyskinesia and axonemal defects confirmed by transmission electronic microscopy (Kott E et al. Am J Hum Genet, 2013 Sep;93:561-70). In addition to the clinical data presented in the literature, 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.

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