ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.832del (p.Ala278fs) (rs727502977)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150491 SCV000197677 likely pathogenic Primary ciliary dyskinesia 2013-11-08 criteria provided, single submitter clinical testing The Ala278fs variant in DNAH5 has been reported in one individual with PCD and o uter dynein arm (ODA) defects who carried a nonsense variant identified on the o ther copy of this gene (Hornef 2006). The variant has not been identified in lar ge population studies. This frameshift variant is predicted to alter the protein 's amino acid sequence beginning at position 278 and lead to a premature termina tion codon 27 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Frameshift and other truncating variants in DN AH5 are associated with autosomal recessive PCD (Hornef 2006). In summary, this variant is likely pathogenic, though additional studies are required to fully es tablish its clinical significance.
Invitae RCV000150491 SCV000826888 pathogenic Primary ciliary dyskinesia 2018-12-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala278Argfs*27) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with primary ciliary dyskinesia (PMID: 16627867). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 163160). Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). For these reasons, this variant has been classified as Pathogenic.

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