rs145381989
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001369.3(DNAH5):c.8862G>T(p.Leu2954=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,613,764 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
DNAH5
NM_001369.3 synonymous
NM_001369.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.13
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 5-13780918-C-A is Benign according to our data. Variant chr5-13780918-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 414346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.13 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.8862G>T | p.Leu2954= | synonymous_variant | 53/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.8862G>T | p.Leu2954= | synonymous_variant | 53/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.8817G>T | p.Leu2939= | synonymous_variant | 53/79 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00110 AC: 167AN: 152194Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000219 AC: 55AN: 250942Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135608
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GnomAD4 exome AF: 0.000116 AC: 170AN: 1461452Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 78AN XY: 727042
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GnomAD4 genome AF: 0.00110 AC: 167AN: 152312Hom.: 2 Cov.: 32 AF XY: 0.00106 AC XY: 79AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 07, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
DNAH5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 13, 2021 | 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at