rs10214399
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001369.3(DNAH5):c.12280-17T>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 0.00158 in 1,599,190 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0088 ( 20 hom., cov: 32)
Exomes 𝑓: 0.00082 ( 13 hom. )
Consequence
DNAH5
NM_001369.3 splice_polypyrimidine_tract, intron
NM_001369.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.43
Genes affected
DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 5-13719118-A-G is Benign according to our data. Variant chr5-13719118-A-G is described in ClinVar as [Benign]. Clinvar id is 257994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13719118-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00883 (1345/152280) while in subpopulation AFR AF= 0.031 (1289/41556). AF 95% confidence interval is 0.0296. There are 20 homozygotes in gnomad4. There are 630 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 20 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.12280-17T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.12280-17T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001369.3 | P4 | |||
DNAH5 | ENST00000681290.1 | c.12235-17T>C | splice_polypyrimidine_tract_variant, intron_variant | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00883 AC: 1344AN: 152162Hom.: 20 Cov.: 32
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GnomAD3 exomes AF: 0.00218 AC: 537AN: 246692Hom.: 12 AF XY: 0.00155 AC XY: 207AN XY: 133530
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GnomAD4 exome AF: 0.000820 AC: 1187AN: 1446910Hom.: 13 Cov.: 27 AF XY: 0.000687 AC XY: 495AN XY: 720904
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GnomAD4 genome ? AF: 0.00883 AC: 1345AN: 152280Hom.: 20 Cov.: 32 AF XY: 0.00846 AC XY: 630AN XY: 74470
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Primary ciliary dyskinesia 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 11, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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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