ClinVar Miner

Submissions for variant NM_001369.3(DNAH5):c.5883-1G>A

gnomAD frequency: 0.00001  dbSNP: rs1195745037
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001382388 SCV001581138 pathogenic Primary ciliary dyskinesia 2023-03-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1070301). Disruption of this splice site has been observed in individual(s) with clinical features of primary ciliary dyskinesia (Invitae). This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change affects an acceptor splice site in intron 35 of the DNAH5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867).
Ambry Genetics RCV001382388 SCV002649485 likely pathogenic Primary ciliary dyskinesia 2015-11-26 criteria provided, single submitter clinical testing The c.5883-1G>A intronic variant results from a G to A one nucleotide upstream from coding exon 36 of the DNAH5 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site predication tools, this alteration is predicted to abolish the native splice acceptor site; although no direct evidence is available. Alterations that disrupt the canonical splice acceptor site are typically deleterious in nature (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). As such, the c.5883-1G>A variant is classified as likely pathogenic.

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