rs114961699
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001369.3(DNAH5):c.3598+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,591,918 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0097 ( 22 hom., cov: 33)
Exomes 𝑓: 0.00095 ( 17 hom. )
Consequence
DNAH5
NM_001369.3 intron
NM_001369.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.170
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 5-13871544-A-G is Benign according to our data. Variant chr5-13871544-A-G is described in ClinVar as [Benign]. Clinvar id is 258020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13871544-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00967 (1473/152314) while in subpopulation AFR AF= 0.0331 (1375/41572). AF 95% confidence interval is 0.0316. There are 22 homozygotes in gnomad4. There are 669 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 22 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.3598+20T>C | intron_variant | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.3598+20T>C | intron_variant | 1 | NM_001369.3 | P4 | |||
ENST00000503244.2 | n.253+10989A>G | intron_variant, non_coding_transcript_variant | 4 | ||||||
DNAH5 | ENST00000681290.1 | c.3553+20T>C | intron_variant | A1 | |||||
ENST00000637153.1 | n.213+11029A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00968 AC: 1474AN: 152196Hom.: 22 Cov.: 33
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GnomAD3 exomes AF: 0.00260 AC: 649AN: 249868Hom.: 6 AF XY: 0.00195 AC XY: 264AN XY: 135068
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GnomAD4 exome AF: 0.000947 AC: 1363AN: 1439604Hom.: 17 Cov.: 28 AF XY: 0.000786 AC XY: 564AN XY: 717752
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GnomAD4 genome ? AF: 0.00967 AC: 1473AN: 152314Hom.: 22 Cov.: 33 AF XY: 0.00898 AC XY: 669AN XY: 74484
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ClinVar
Significance: Benign
Submissions summary: Benign:2
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 | - - |
Computational scores
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Name
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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