14-73654842-TA-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePM2BP6
The NM_031427.4(DNAL1):c.4-2delA variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000778 in 1,336,952 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000078 ( 0 hom. )
Consequence
DNAL1
NM_031427.4 splice_acceptor, intron
NM_031427.4 splice_acceptor, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0200
Genes affected
DNAL1 (HGNC:23247): (dynein axonemal light chain 1) This gene encodes an axonemal dynein light chain which functions as a component of the outer dynein arms complex. This complex acts as the molecular motor that provides the force to move cilia in an ATP-dependent manner. The encoded protein is expressed in tissues with motile cilia or flagella and may be involved in the movement of sperm flagella. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.066317625 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.3, offset of 0 (no position change), new splice context is: ttcttttttttttttttaAGgcg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 14-73654842-TA-T is Benign according to our data. Variant chr14-73654842-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 3353166.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DNAL1 | NM_031427.4 | c.4-2delA | splice_acceptor_variant, intron_variant | ENST00000553645.7 | NP_113615.2 | |||
| DNAL1 | NM_001201366.2 | c.-114-2delA | splice_acceptor_variant, intron_variant | NP_001188295.1 | ||||
| DNAL1 | XM_017021679.3 | c.-114-2delA | splice_acceptor_variant, intron_variant | XP_016877168.1 | ||||
| DNAL1 | XM_024449715.2 | c.-114-2delA | splice_acceptor_variant, intron_variant | XP_024305483.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.0000778 AC: 104AN: 1336952Hom.: 0 Cov.: 33 AF XY: 0.0000683 AC XY: 45AN XY: 658654
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33
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45
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658654
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GnomAD4 genome
GnomAD4 genome
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31
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
DNAL1-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 18, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at