rs72658832
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001277115.2(DNAH11):c.13163-19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,612,826 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0032 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0042 ( 28 hom. )
Consequence
DNAH11
NM_001277115.2 intron
NM_001277115.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.534
Genes affected
DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]
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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=-0.86).
BP6
?
Variant 7-21899961-T-A is Benign according to our data. Variant chr7-21899961-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 257869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00321 (488/152240) while in subpopulation SAS AF= 0.0085 (41/4826). AF 95% confidence interval is 0.00644. There are 2 homozygotes in gnomad4. There are 238 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.13163-19T>A | intron_variant | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.13163-19T>A | intron_variant | 5 | NM_001277115.2 | P1 | |||
DNAH11 | ENST00000479878.1 | n.534-19T>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00321 AC: 489AN: 152122Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00422 AC: 1045AN: 247470Hom.: 8 AF XY: 0.00475 AC XY: 638AN XY: 134258
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GnomAD4 exome AF: 0.00416 AC: 6082AN: 1460586Hom.: 28 Cov.: 31 AF XY: 0.00445 AC XY: 3232AN XY: 726542
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GnomAD4 genome ? AF: 0.00321 AC: 488AN: 152240Hom.: 2 Cov.: 33 AF XY: 0.00320 AC XY: 238AN XY: 74434
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
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 30, 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 31, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 28, 2017 | - - |
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