rs141389162
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001369.3(DNAH5):c.6579+6A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,886 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0074 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00071 ( 15 hom. )
Consequence
DNAH5
NM_001369.3 splice_donor_region, intron
NM_001369.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00002931
2
Clinical Significance
Conservation
PhyloP100: -0.390
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=-0.81).
BP6
?
Variant 5-13824193-T-C is Benign according to our data. Variant chr5-13824193-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 226604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13824193-T-C is described in Lovd as [Benign]. Variant chr5-13824193-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00736 (1121/152244) while in subpopulation AFR AF= 0.0258 (1071/41530). AF 95% confidence interval is 0.0245. There are 12 homozygotes in gnomad4. There are 512 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.6579+6A>G | splice_donor_region_variant, intron_variant | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.6579+6A>G | splice_donor_region_variant, intron_variant | 1 | NM_001369.3 | P4 | |||
DNAH5 | ENST00000681290.1 | c.6534+6A>G | splice_donor_region_variant, intron_variant | A1 | |||||
DNAH5 | ENST00000683090.1 | n.1510+6A>G | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00734 AC: 1116AN: 152126Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00192 AC: 482AN: 251268Hom.: 5 AF XY: 0.00149 AC XY: 203AN XY: 135806
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GnomAD4 exome AF: 0.000707 AC: 1034AN: 1461642Hom.: 15 Cov.: 31 AF XY: 0.000619 AC XY: 450AN XY: 727130
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GnomAD4 genome ? AF: 0.00736 AC: 1121AN: 152244Hom.: 12 Cov.: 32 AF XY: 0.00688 AC XY: 512AN XY: 74440
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | 6579+6A>G in intron 39 of DNAH5: This variant is not expected to have clinical s ignificance because it has been identified in 2.5% (108/4406) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs141389162). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Primary ciliary dyskinesia 3 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 06, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 21, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Primary ciliary dyskinesia Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
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