rs149634292
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001277115.2(DNAH11):c.13050-15C>T 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 0.000689 in 1,607,266 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 7 hom. )
Consequence
DNAH11
NM_001277115.2 splice_polypyrimidine_tract, intron
NM_001277115.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.234
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 7-21899321-C-T is Benign according to our data. Variant chr7-21899321-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 227320.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00373 (568/152284) while in subpopulation AFR AF= 0.0128 (532/41548). AF 95% confidence interval is 0.0119. There are 0 homozygotes in gnomad4. There are 268 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.13050-15C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.13050-15C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001277115.2 | P1 | |||
DNAH11 | ENST00000479878.1 | n.421-15C>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00366 AC: 557AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000895 AC: 223AN: 249112Hom.: 3 AF XY: 0.000607 AC XY: 82AN XY: 135164
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GnomAD4 exome AF: 0.000370 AC: 539AN: 1454982Hom.: 7 Cov.: 28 AF XY: 0.000319 AC XY: 231AN XY: 724384
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 14, 2016 | c.13050-15C>T in intron 79 of DNAH11: This variant is not expected to have clini cal significance because it has been identified in 1.2% (123/9800) of African ch romosomes, including 1 homozygote, by the Exome Aggregation Consortium (ExAC, ht tp://exac.broadinstitute.org; dbSNP rs149634292). - |
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