chr14-73671555-ATTATCTT-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_031427.4(DNAL1):c.224_230delTATCTTT(p.Leu75fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000201 in 1,492,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_031427.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAL1 | NM_031427.4 | c.224_230delTATCTTT | p.Leu75fs | frameshift_variant | Exon 5 of 8 | ENST00000553645.7 | NP_113615.2 | |
DNAL1 | NM_001201366.2 | c.107_113delTATCTTT | p.Leu36fs | frameshift_variant | Exon 6 of 9 | NP_001188295.1 | ||
DNAL1 | XM_017021679.3 | c.107_113delTATCTTT | p.Leu36fs | frameshift_variant | Exon 6 of 9 | XP_016877168.1 | ||
DNAL1 | XM_024449715.2 | c.107_113delTATCTTT | p.Leu36fs | frameshift_variant | Exon 6 of 9 | XP_024305483.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32
GnomAD4 exome AF: 7.46e-7 AC: 1AN: 1340554Hom.: 0 AF XY: 0.00000151 AC XY: 1AN XY: 663860
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 16 Pathogenic:1
This sequence change creates a premature translational stop signal (p.Leu75*) in the DNAL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAL1 are known to be pathogenic (PMID: 21496787). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 228252). This variant has not been reported in the literature in individuals affected with DNAL1-related conditions. This variant is not present in population databases (gnomAD no frequency). -
Primary ciliary dyskinesia Pathogenic:1
The p.Leu36X variant in DNAL1 has not been previously reported in individuals wi th pulmonary disease or in large population studies. This variant is a deletion of 7 nucleotides at position 107 and is predicted to alter the protein reading-f rame, resulting in a premature termination codon at amino acid position 36. This alteration is then predicted to lead to a truncated or absent protein. In summa ry, although additional studies are required to fully establish its clinical sig nificance, the p.Leu36X variant is likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at