ClinVar Miner

Submissions for variant NM_001277115.2(DNAH11):c.11203-1G>C

dbSNP: rs1783074775
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001245195 SCV001418466 pathogenic Primary ciliary dyskinesia 2023-08-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 68 of the DNAH11 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 DNAH11 are known to be pathogenic (PMID: 18022865, 20513915, 22184204). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with primary ciliary dyskinesia (PMID: 31772028; Invitae). ClinVar contains an entry for this variant (Variation ID: 969771). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001245195 SCV002746871 likely pathogenic Primary ciliary dyskinesia 2016-03-25 criteria provided, single submitter clinical testing The c.11203-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 69 of the DNAH11 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 6106 samples (12212 alleles) with coverage at this position. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP splice site prediction tool, 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.11203-1G>C variant is classified as likely pathogenic.

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