chr7-21868996-G-A
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001277115.2(DNAH11):c.11967+5G>A variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001277115.2 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- primary ciliary dyskinesia 7Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
For these reasons, this variant has been classified as Likely Pathogenic. This variant occurs with a Pathogenic variant (p.Arg1541*) in DNAH11 in an individual with phenotype consistent with primary ciliary dyskinesia. While it is unknown if these two variants are on the same or opposite chromosomes, this observation suggests that the c.11967+5G>A variant may contribute to the cause of disease. Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this intronic variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DNAH11-related disease. This sequence change falls in intron 73 of the DNAH11 mRNA. It does not directly change the encoded amino acid sequence of the DNAH11 protein. This variant affects a highly conserved nucleotide within the consensus splice site of intron 73. The majority of introns (75%) have a guanine at this position (PMID: 9536098). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at