rs201880561
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_031427.4(DNAL1):c.153-12G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,533,590 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00039 ( 4 hom. )
Consequence
DNAL1
NM_031427.4 splice_polypyrimidine_tract, intron
NM_031427.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00004958
2
Clinical Significance
Conservation
PhyloP100: 1.16
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 14-73661975-G-C is Benign according to our data. Variant chr14-73661975-G-C is described in ClinVar as [Benign]. Clinvar id is 261957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73661975-G-C is described in Lovd as [Likely_benign].
BS2
?
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAL1 | NM_031427.4 | c.153-12G>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000553645.7 | |||
DNAL1 | NM_001201366.2 | c.36-12G>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
DNAL1 | XM_017021679.3 | c.36-12G>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
DNAL1 | XM_024449715.2 | c.36-12G>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAL1 | ENST00000553645.7 | c.153-12G>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_031427.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00390 AC: 593AN: 151894Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00109 AC: 164AN: 150196Hom.: 2 AF XY: 0.000835 AC XY: 66AN XY: 79018
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GnomAD4 exome AF: 0.000388 AC: 536AN: 1381578Hom.: 4 Cov.: 29 AF XY: 0.000325 AC XY: 221AN XY: 680884
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GnomAD4 genome ? AF: 0.00390 AC: 593AN: 152012Hom.: 4 Cov.: 32 AF XY: 0.00367 AC XY: 273AN XY: 74302
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 16 Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at